Lipoprotein a Research Papers - Academia.edu (original) (raw)

2025, Blood Coagulation & Fibrinolysis

Several studies have suggested that thrombophilic risk factors are more prevalent in individuals with idiopathic intracranial hypertension (IIH), and that a prothrombic state may be involved in the etiopathogenesis of this disease. We examine thrombophilic factors in a group of patients with IIH in relation to obesity. In addition, we reviewed the relevant literature and performed a meta-analysis. Thrombophilia work-up was performed on 51 patients with IIH at least 1 month following their first episode. Samples for the analysis of factor V Leiden (FVL), prothrombin gene variant (PGV) G20210A and methylenetetrahydrofolate reductase (MTHFR) were available in an additional 30 patients, that is 81 patients in all. Meta-analysis was performed. Of the 51 patients 40 were obese. Increased concentrations of fibrinogen, D-Dimer, factor VIII, factor IX and factor XI were found in 15, 7, 7, 6 and 2 patients, respectively, all obese. The circulating anticoagulant, measured by dilute Russell's viper venom time (dRVVT assay), found mainly in obese. All 51 patients were negative for the anticardiolipin antibody (IgG immunoglobulin G) and IgG anti-b2 glycoprotein I. In the meta-analysis antiphospholipid antibodies were significantly associated with IIH [odds ratio (OR) of 4.25 (1.68-12.60)], similar to the association with high factor VIII [OR U 16.17 (2.87-91.01)], higher plasminogen activator inhibitor-1 (PAI-1) levels [OR U 6.91 (2.28-20.91)], and high lipoprotein (a) [LP(a)] [OR U 3.54 (1.54-8.70)]. Obesity often observed in IIH patients is frequently linked with thrombophilic factors. Thus, we believe that dysmetabolism could be the thrombophilic target for treatment in patients with IIH.

2025, Investigative Opthalmology & Visual Science

To determine associations between retinopathy status and detailed serum lipoprotein subclass profiles in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) cohort. METHODS. Persons with type 1 diabetes (440 women, 548 men) from the DCCT/EDIC cohort were studied. Retinopathy was characterized by Early Treatment Diabetic Retinopathy Study (ETDRS) scores, hard exudate scores, and ETDRS scores minus the hard exudate component. Lipoproteins were characterized by conventional lipid profile, nuclear magnetic resonance lipoprotein subclass profile (NMR-LSP), apoA1, apoB, lipoprotein(a), and susceptibility of LDL to oxidation. Data were analyzed with and without the following covariates: age, gender, duration of diabetes, HbA 1c , albumin excretion rate (AER), creatinine clearance, hypertension, body mass index, waist-hip ratio, DCCT treatment group, smoking status. RESULTS. The severity of retinopathy was positively associated with triglycerides (combined cohort) and negatively associated with HDL cholesterol (men, combined cohort). NMR-LSP iden-tified retinopathy as being positively associated with small and medium VLDL and negatively with VLDL size. In men only, retinopathy was positively associated with small LDL, LDL particle concentration, apoB concentration, and small HDL and was negatively associated with large LDL, LDL size, large HDL, and HDL size. No associations were found with apoA1, Lp(a), or susceptibility of LDL to oxidation. All three measures of retinopathy revealed the same associations. CONCLUSIONS. NMR-LSP reveals new associations between serum lipoproteins and severity of retinopathy in type 1 diabetes. The data are consistent with a role for dyslipoproteinemia involving lipoprotein subclasses in the pathogenesis of diabetic retinopathy. (Invest

2025, Diabetes Care

OBJECTIVE—To relate the nuclear magnetic resonance (NMR)-determined lipoprotein profile, conventional lipid and apolipoprotein measures, and in vitro oxidizibility of LDL with gender and glycemia in type 1 diabetes. RESEARCH DESIGN AND METHODS—In the 1997–1999 Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort, serum from 428 women and 540 men were characterized by conventional lipids, NMR, apolipoprotein levels, and LDL susceptibility to in vitro oxidation. Simple and partial correlation coefficients were calculated for each lipoprotein-related parameter versus gender, with and without covariates (age, diabetes duration, concurrent HbA1c, DCCT randomization, hypertension, BMI, waist-to-hip ratio, and albuminuria). For concurrent HbA1c, data were analyzed as above, exchanging gender for HbA1c. Associations were significant if P < 0.05. RESULTS—Although men and women had similar total and LDL cholesterol and triglyce...

2025, Diabetes Research and Clinical Practice

2025, Atherosclerosis Supplements

Background: Statins are well tolerated but a minority of patients suffer side effects, commonly muscle pain, and discontinue therapy. Myalgia/myositis occur with all statins and are more common with higher doses. Rosuvastatin is the most potent statin, and 5 mg daily can lower LDL cholesterol by ∼ 40%. Since Rosuvastatin has the longest half life (19 hours) of any statin, it is possible to use it on an alternate day basis. We have studied the tolerability and efficacy of low dose alternate day Rosuvastatin in patients previously intolerant of statins. Methods: 11 consecutive patients (6 male, 5 female, age 62.3 (11.3) years [mean, (SD)]) attending our Lipid Clinic with primary hypercholesterolaemia and high CVD risk, and who had been unable to tolerate statins were given Rosuvastatin 5 mg every second day. Results: All had normal thyroid function. Baseline serum CPK was 228 (50 -2173) U/L [median, (range)] and 6 had a serum CPK > 200 U/L. None had experienced rhabdomyolysis. All had used statins in conventional doses but had discontinued therapy < 3 months, mostly because of myalgia. 7 were able to take Ezetimibe. Total cholesterol was 8.37 (1.02) mmol/L [mean, (SD)] at baseline and 4.41 (1.01) mmol/L on alternate day Rosuvasatin (± Ezetimibe), a 47% reduction. Serum CPK was 164 (109 -1532) U/L on Rosuvastatin (± Ezetimibe). Conclusion: All patients tolerated low dose Rosuvastatin without side effects. Low dose alternate day Rosuvastatin is effective and well tolerated in patients previously unable to take statins.

2025, Nutrition Metabolism and Cardiovascular Diseases

Background and Aims: Epidemiological studies suggest that regular consumption of cocoa-containing products may confer cardiovascular protection, reducing the risk of coronary heart disease (CHD). However, studies on the effects of cocoa on different cardiovascular risk factors are still scarce. The aim of this study was too evaluate the effects of chronic cocoa consumption on lipid profile, oxidized low-density lipoprotein (oxLDL) particles and plasma antioxidant vitamin concentrations in high-risk patients. Methods and Results: Forty-two high-risk volunteers (19 men and 23 women, mean age 69.7 AE 11.5 years) were included in a randomized, crossover feeding trial. All received 40g of cocoa powder with 500 mL of skimmed milk/day(C þ M) or only 500 mL/day of skimmed milk (M) for 4 weeks in a random order. Before and after each intervention period, plasma lipids, oxLDL and antioxidant vitamin concentrations were measured, as well as urinary cocoa polyphenols metabolites derived from phase II and microbial metabolisms. Compared to M, C þ M intervention increases HDLc [2.67 mg/dL (95% confidence intervals, CI, 0.58e4.73

2025, Kidney International

Lipoprotein(a) in nephrotic syndrome. Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease, and it has also been speculated that it promotes thrombosis. Recent studies have shown that patients with gross proteinuria have greatly increased plasma levels of Lp(a), but the genesis is obscure. In the present study, plasma Lp(a) levels were measured in 31 patients with nephrotic syndrome (NS), 24 patients with IgA nephropathy and 43 healthy control subjects. Lp(a) levels were significantly elevated in NS (median 49.0 mg/dl), in contrast to the control subjects and patients with IgA nephropathy (median 7.0 and 9.7 mg/dl, respectively). Plasma Lp(a) levels fell markedly in 10 of 10 NS patients after remission. In NS, Lp(a) levels correlated directly with serum cholesterol levels (P < 0.05) and indirectly with plasma orosomucoid levels (P < 0.05), but not with serum albumin, triglycerides, HDL cholesterol, urinary protein excretion or GFR. In addition, Lp(a) tended to be higher in NS patients with edema (median 54.3 mgldl) than in patients without edema (19.0 mg/dl; P = 0.06). Nine NS patients were further evaluated with plasma ANP levels and urinary sodium excretion. Plasma Lp(a) correlated directly with ANP (P < 0.01) and indirectly with urinary sodium excretion (P < 0.05). Excellent correlations were found between Lp(a) and VLDL cholesterol and VLDL triglycerides, respectively, suggesting a close link between Lp(a) and triglyceride-rich lipoproteins in nephrosis. Hyperlipidemia is a common feature of nephrotic syndrome (NS) and is often included in the definition of the condition . Both increased synthesis and decreased clearance of lipoproteins may contribute to the hyperlipidemia usually characterized by increases in the total and low-density lipoprotein (LDL) cholesterol levels, with normal or reduced high-density lipoprotein (HDL) cholesterol . In non-nephrotic patients this type of lipid abnormality is associated with accelerated atherosclerosis [31. Furthermore, a considerably increased incidence of coronary heart disease has been reported in patients with NS . Lipoprotein(a) [Lp(a)] is a plasma lipoprotein, originally described by Berg [6], consisting of a particle similar to lowdensity lipoprotein (LDL), with apoprotein (a) covalently linked to apoprotein B-l00 by a disulphide bridge . Plasma apo(a) levels vary several hundred-fold in the population, and an inverse relation between the molecular size of apo(a) and its plasma levels has been found . Moreover, recent studies have demonstrated that a major part (90%) of the interindi-

2025, Urologia Internationalis

Introduction: To determine the changes in plasma lipid levels in symptomatic benign prostatic hyperplasia (BPH) patients receiving terazosin treatment. Materials and Methods: The study included 99 patients with BPH aged 44–74 years. The patients were divided into 3 groups: in group 1 (n = 25) with baseline total cholesterol levels of >220 mg/dl, terazosin 5 mg/day was used; in group 2 (n = 56) with basal total cholesterol levels of < 220 mg/dl, terazosin 5 mg/day was used, and group 3 (n = 18) did not use terazosin and was defined as the control group. Plasma levels of total cholesterol, low-density lipoprotein, high-density lipoprotein and triglyceride were recorded, and the high-density lipoprotein to total cholesterol ratio was calculated at the beginning of the study and after 12 weeks. Results: The total cholesterol level decreased from the baseline level by 10.88% after 12 weeks (p < 0.05) in group 1. The decrease was observed in 22 of 25 patients (88%). In group 1, t...

2025, Atherosclerosis

Methods: We examined 299 patients (mean age 68.8 ± 9.2 years) with significant peripheral and carotid atherosclerotic lesions (stenosis above 50% in at least one peripheral and/or carotid artery), and 179 of them with isolated lesions of peripheral or carotid arteries have been divided into 2 groups. The first group (n¼47) consisted those with stenotic lesions of peripheral arteries. Patients (n¼132) with stenotic lesions of carotid arteries formed the second group. Coronary heart disease was proved in 145 (81%) patients. The level of Lp(a) has been measured by enzyme-linked immunosorbent assay. Results: Both groups were comparable in clinical and biochemical characteristics. In the first group the level of Lp(a) was 62 ± 53 mg/dl versus the second group e 39 ± 42 mg/dl (p¼0.003). The number of patients with Lp(a) level >30 mg/dl was significantly more in the first group: 31 (66%) compared to 53 (40%), p¼0.0045. Current smoking was more frequent in the group I: 20 (43%) compared to 24 (18%), p¼0.002. Conclusions: Being an acknowledged cardiovascular risk factor, Lp(a) may be considered as an important discriminator of severe peripheral atherosclerosis.

2025

Diabetes is a metabolic disorder characterized by hyperglycemia, either due to insulin deficiency or insulin resistance. Despite some progress in the development of new anti-diabetic agents, the ability to maintain tight glycemic control in order to prevent complications of diabetes without adverse complications still remains a challenge. In present study100 type 2 diabetic patients and 100 age and sex matched control subjects were included. We investigated the blood glucose, lipoproteins, atherogenic ratios and glycosylated haemoglobin in study and control group. Further the type 2 diabetic subjects were divided in to two groups depending on glycemic index, first group consists of patients with HbA1c level ≤7.0 % and second group consists of patients with HbA1c level>7.0%. We found significant increase in the levels of total serum cholesterol, triglyceride, LDL cholesterol and VLDL cholesterol in patients with type 2 diabetes than control subjects. Also the atherogenic ratios vi...

2025, European Journal of Paediatric Neurology

Phakomatosis pigmentovascularis is a rare congenital cutaneous malformation syndrom characterised by vascular and melanocytic components. According to findings of dermal or systemic, four types have been recognised. Sturge Weber syndrome is a rare neurocutaneous disorder characterised by port-wine nevus, leptomeningeal angiomatosis, choroidal vascular lesions and neurologic detoriation. In this article, we report a case of phakomatosis pigmentovascularis type IIb associated with Sturge-Weber syndrome from Turkey. Case: A three months old girl was admitted to our clinic with complaints of cyanosis and congenital vascular and pigmentary cutaneous lesions. At one-month-old-age, she was operated for bilaterally glaucoma in another clinic. Cranial tomography of the patient was normal at two months old. At the admission, there were vascular lesions over the face and melanocytic lesions over the trunk and extremities. Cranial tomography showed calcification in the right parietal region, cerebral atrophy. Cranial MRI revealed right serebral atrophy, diffuse pial enhancement in right serebral hemisphere and the left temporo-oksipital region. The association of Phakomatosis pigmentovascularis tip IIb with Sturge-Weber syndrome is very rare. Cerebral atrophy may occur very quickly in this case. For that reason, this patients must be frequently evaluated for occurrence of serebral atrophy and leptomeningeal angiomatosis.

2025, Revista Peruana de Medicina Experimental y Salud Pública

Bothrops sp. snakes causing the largest number of cases of ophidism in Peru, their venom contain several enzymes related to poison spreading, miotoxic and platelet aggregation disturbances. Objectives. The inhibiting capacity of liquid polivalent bothropic antivenom from Instituto Nacional de Salud (INS) has been evaluated on phospholipase A 2 (PLA2), L amino acid oxidase (LAO) and hyaluronidase activities using B. atrox, B. barnetti, B. brazili and B. pictus venoms. Material and methods. In each case on 45% egg yolk lipoprotein, Lleucina and O-dianisidine, as well as hyaluronic acid as substrates respectively, using for each enzyme ½, 1 and 2 doses of either natural and heated (37 °C during five days) antivenom, assayed in triplicate. Results. HA was more neutralized enzyme for antivenin, all venoms with the exception of B. brazili were totally inhibited at any dose. For LAO had values of inhibition of 68 to 100% using two doses of the antivenin, PLA2 was the least inhibited (70 to...

2025, Free Radical Biology and Medicine

The consumption of red wine has been reported to impart a greater benefit in the prevention of coronary heart disease than the consumption of other alcoholic beverages. This beneficial effect is increasingly being attributed to certain antioxidants comprising the polyphenol fraction of red wine such as transresveratrol. In the present study, we investigated the potential cardioprotective effects of resveratrol in the face of ischemia reperfusion (I/R) injury. Isolated perfused working rat hearts after stabilization were perfused with Krebs-Henseleit Bicarbonate buffer (KHB) either in the presence or absence of transresveratrol (RVT) at a concentration of 10 M for 15 min prior to subjecting them to 30 min of global ischemia followed by 2 h of reperfusion. Left ventricular functions were monitored at various timepoints throughout the reperfusion period to assess the extent of postischemic recovery in comparison with baseline values. Coronary perfusate samples were also collected to determine malonaldehyde (MDA) levels. The results demonstrated that RVT exhibited significant myocardial protection. This was evidenced by improved recovery of post-ischemic ventricular function including developed pressure and aortic flow as compared to the control group (KHB). Values for developed pressure in the RVT-treated group were significantly higher than those in the control group throughout the reperfusion period (71.09

2025, Pharmacological Research

Pomegranate (Punica granatum L.) juice (PJ) is being increasingly proposed as a nutritional supplement to prevent atherosclerosis in humans. This therapeutically valuable potential has been attributed to PJ antioxidant capacity which has been mostly tested by means of cell-free assays: indeed, to the best of our knowledge, no study has focused on the direct antioxidant capacity of PJ in cultured cells. Here, the antioxidant capacity in cell free-systems of preparations from various parts of pomegranate has been compared with their cytoprotectivebona fide antioxidant -activity in cultured human cells (U937 promonocytes and HUVEC endothelial cells) exposed to an array of oxidizing agents. Pomegranate derivatives were PJ, arils only juice (AJ) and aqueous rinds extract (RE). In cell-free assays -1,1-diphenyl-2-picrylhydrazyl (DPPH), chemiluminescence luminol/xanthine/xanthine oxidase and lipoxygenase assays -all the preparations displayed good antioxidant capacity, the relative potency order being RE > PJ > AJ. On the contrary, only RE was capable of preventing the deleterious effects -cytotoxicity, DNA damage and depletion of nonprotein sulphydrils (NPSH) pool -caused by treatment of cells with H 2 O 2 , tert-butylhydroperoxide (tB-OOH) or oxidized lipoproteins (Ox-LDL) via a mechanism which is likely to involve both direct scavenging of radical species and iron chelation. Surprisingly, AJ and PJ slightly sensitized cells to the cytotoxic effects of the three agents. Then it would appear that AJ, the major and tasty part of PJ, does not contain ellagic acid and punicalagin (i.e. the polyphenols highly represented in RE which are reputed to be responsible for the antioxidant capacity) in amounts sufficient to exert cytoprotection in oxidatively injured, living cells. Based on these results, the development and evaluation of rinds-only based derivatives for antiatherogenic preventive purposes in humans should be encouraged.

2025, Veterinary Parasitology

In this work we describe the internal morphology of the female reproductive system of the cayenne tick Amblyomma cajennense. This system is represented by a panoistic ovary, which lacks nurse cells in the germarium. This ovary consists of a single tube, in which a large number of oocytes develop asynchronously, thus accompanying the processes of yolk deposition in the oocytes. The oocytes were classified into stages that varied from I to V, according to: cytoplasm appearance, presence of the germ vesicle, presence of yolk granules, and presence of chorion. The study of vitellogenesis dynamics suggest that the yolk elements are deposited in the oocyte following a preferencial sequence, in which the lipids are the first to appear, followed by proteins an finally by the carbohydrates. In this way the yolk of A. cajennense ticks have these three elements that may be free in the cytoplasm or chemically bounded forming glycoprotein or lipoprotein complexes.

2025, The Journal of Pediatrics

To determine whether coronary artery calcification (CAC), elevated fasting lipids, and lipoproteins and peripheral inflammatory markers are present in insulin-dependent diabetic adolescents and young adults several years after diagnosis. Study design Hispanic insulin-dependent diabetics (n ‫؍‬ 32) diagnosed a mean of 7.8 ؎ 4.5 years ago (range, 3 to 16 years), with a mean glycosylated hemoglobin concentration at the time of the study of 8.8% ؎ 2.3% and a mean chronological age of 16.1 ؎ 4.4 years, were evaluated. Healthy patients (n ‫؍‬ 15) with a chronological age (CA) of 15.2 ؎ 2.2 years served as control subjects. CAC was assessed by multiple slice computed tomography, and total CAC score in Agatston units was calculated. Fasting lipids, C-reactive protein, apolipoprotein (Apo) A, Apo B, and metalloproteinase-9 (MMP-9) concentrations were measured in all subjects. Results Neither adolescents with type 1 diabetes nor healthy control subjects presented with evidence of CAC. Fasting lipids, Apo A, Apo B, CRP, and MMP-9 concentrations were similar between diabetic subjects and control subjects. However, 34.4% and 25.0% of our type 1 diabetic subjects had elevated total and LDL cholesterol levels (>200 and >130 mg/dL, respectively), whereas 15.6% and 28.1% had elevated triglyceride and Apo B concentrations (>150 mg/dL and >100 mg/dL, respectively). In addition, 28.1% and 34.4% presented with elevated CRP and MMP-9 levels (>2 mg/L and >80 ng/mL, respectively). Total, LDL and HDL cholesterol, triglycerides, Apo B, CRP, and MMP-9 concentrations correlated positively with duration of the disease and with glycosylated hemoglobin levels. Although the study adolescents with type 1 diabetes did not present any radiologic evidence of CAC at this stage of the disease, they remain a high-risk group for the development of microvascular and macrovascular artery disease, as risk factors such as elevated lipoproteins and proinflammatory markers are already present in a significant percentage of patients studied. (J Pediatr 2006;149:320-3) Apo Apolipoprotein CAC Coronary artery calcification CRP C-reactive protein EBCT Electron-beam computed tomography IMT Intima-media thickness MMP-9 Matrix metalloproteinase-9

2025, Revista Española de Cardiología (English Edition)

To detect differences of 4% (eg, 50%-54%) in visit estimations, in a situation of maximum lack of determination (p=q=0.5), with a precision (alpha) of .05 and a statistical power (1-beta) of .8, the number

2025, Journal of Clinical Lipidology

2025, Kidney International

The apolipoprotein(a) size polymorphism is associated with nephrotic syndrome. Background. The atherogenic serum lipoprotein(a) [Lp(a)] is significantly elevated in patients with nephrotic syndrome. The underlying mechanism for this elevation is poorly understood. Methods. We investigated in 207 patients with nondiabetic nephrotic syndrome and 274 controls whether the apolipoprotein(a) [apo(a)] kringle-IV repeat polymorphism explains the elevated Lp(a) levels in these patients. Results. Patients showed a tremendous elevation of Lp(a) concentrations when compared to controls (mean 60.4 vs. 20.0 mg/dL and median 29.8 vs. 6.4 mg/dL, P < 0.0001). Primary and secondary causes contributed to this elevation. The primary causes became apparent by a markedly elevated number of low-molecular-weight apo(a) phenotypes which are usually associated with high Lp(a) levels. This frequency was 35.7% in patients compared to only 24.8% in controls (P = 0.009). In addition, secondary causes by the pathogenetic mechanisms of the nephrotic syndrome itself resulted in a different increase of Lp(a) in the various apo(a) isoform groups. Based on the measured Lp(a) concentrations in each subject, we calculated separately the Lp(a) concentrations arising from the two expressed isoforms by estimating the relative proportion of the two serum isoforms in the sodium dodecyl sulfate (SDS) agarose gel electrophoresis. Low-molecular-weight isoforms were associated with 40% to 75% elevated Lp(a) concentrations when compared to matched isoforms from controls. High-molecularweight apo(a) isoforms showed 100% to 500% elevated Lp(a) levels compared to matched isoforms from controls. The severity of the nephrotic syndrome as well as the degree of renal impairment did not influence the Lp(a) concentrations.

2025, Cardiovascular Research

The relevance of lipoprotein(a) [Lp(a)] concentrations and low-molecular-weight (LMW) apo(a) phenotypes in peripheral arterial disease (PAD) has only been investigated by few studies. Therefore, we analysed this association in three independent cohorts and performed a Mendelian Randomization approach using instrumental variable regression. Lp(a) concentrations, apo(a) phenotypes, and one SNP in the LPA gene (rs10455872) were measured in the CAVASIC study, including 241 male patients with intermittent claudication and 246 age-and diabetes-matched controls as well as in the two population-based studies KORA F3 (n ¼ 3184) and KORA F4 (n ¼ 3080). In KORA F3/F4, 109/80 persons suffered from intermittent claudication, 200/144 from PAD, and 128/103 showed an ankle-brachial index (ABI) ,0.9. In CAVASIC, adjusted logistic regression analyses revealed significant associations between an increase of log-Lp(a) per one standard deviation (SD) (OR ¼ 1.28, P ¼ 0.02) as well as LMW apo(a) phenotypes and symptomatic PAD (OR ¼ 1.65, P ¼ 0.03). Linear regression models with continuous ABI showed a significant association in the combined analyses of KORA F3/F4: an increase in log-Lp(a) per one SD (b ¼ 20.006, P ¼ 0.005) and the presence of LMW apo(a) phenotypes (b ¼ 20.011, P ¼ 0.02) or the minor allele of rs10455872 (ß ¼ 20.016, P ¼ 0.03) were associated with a decrease in ABI in the fully adjusted linear and instrumental variable regression models. Analyses in three independent populations showed significant associations of Lp(a) concentrations, LMW apo(a) phenotypes, and rs10455872 with PAD. This points to a causal relationship between Lp(a) and PAD since the genetically determined apo(a) phenotypes and SNP alleles are indeed associated with PAD.

2025, Current Cardiovascular Risk Reports

Recent proteomics studies on human plasma high-density lipoprotein (HDL) have discovered up to 50 individual protein constituents. Many of these have known functions that vary surprisingly from the lipid transport roles commonly thought to mediate HDL's ability to protect from coronary artery disease. Given newly discovered roles in inflammation, protease inhibition, complement regulation, and innate immunity, many have begun to view HDL as a broad collection of distinct particle subfamilies, each distinguished by unique protein compositions and functions. Herein we review recent applications of high-resolution proteomics to HDL and summarize evidence supporting the idea of HDL functional subspeciation. These studies have set the stage for a more complete understanding of the molecular basis of HDL functional heterogeneity and hold promise for the identification of new biomarkers that can predict disease or evaluate the success of clinical interventions.

2025, Journal of Lipid Research

Atorvastatin, a synthetic HMG-CoA reductase inhibitor used for the treatment of hyperlipidemia and the prevention of coronary artery disease, significantly lowers plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. It also reduces total plasma triglyceride and apoE concentrations. In view of the direct involvement of apoE in the pathogenesis of atherosclerosis, we have investigated the effect of atorvastatin treatment (40 mg/day) on in vivo rates of plasma apoE production and catabolism in six patients with combined hyperlipidemia using a primed constant infusion of deuterated leucine. Atorvastatin treatment resulted in a significant decrease (i.e., 30-37%) in levels of total triglyceride, cholesterol, LDL-C, and apoB in all six patients. Total plasma apoE concentration was reduced from 7.4 ؎ 0.9 to 4.3 ؎ 0.2 mg/dl ( Ϫ 38 ؎ 8%, P Ͻ 0.05), predominantly due to a decrease in VLDL apoE (3.4 ؎ 0.8 vs. 1.7 ؎ 0.2 mg/dl; ؊ 42 ؎ 11%) and IDL/LDL apoE (1.9 ؎ 0.3 vs. 0.8 ؎ 0.1 mg/dl; Ϫ 57 ؎ 6%). Total plasma lipoprotein apoE transport (i.e., production) was significantly reduced from 4.67 ؎ 0.39 to 3.04 ؎ 0.51 mg/kg/day ( ؊ 34 ؎ 10%, P Ͻ 0.05) and VLDL apoE transport was reduced from 3.82 ؎ 0.67 to 2.26 ؎ 0.42 mg/kg/day ( ؊ 36 ؎ 10%, P ‫؍‬ 0.057). Plasma and VLDL apoE residence times and HDL apoE kinetic parameters were not significantly affected by drug treatment. Percentage decreases in VLDL apoE concentration and VLDL apoE production were significantly correlated with drug-induced reductions in VLDL triglyceride concentration ( r ‫؍‬ 0.99, P Ͻ 0.001; r ‫؍‬ 0.88, P Ͻ 0.05, respectively, n ‫؍‬ 6). Our results demonstrate that atorvastatin causes a pronounced decrease in total plasma and VLDL apoE concentrations and a significant decrease in plasma and VLDL apoE rates of production in patients with combined hyperlipidemia.

2025, Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

IntroductionLipoprotein‐associated phospholipase A2 (Lp‐PLA2) and homocysteine (Hcy) have been linked to inflammation and Alzheimer's disease (AD). Using a case‐control design, we examined their independent effects and interactions with cardiovascular disease equivalent (CVDE), on AD risk.MethodsAD cases and controls were from the Texas Alzheimer's Research and Care Consortium study. Lp‐PLA2 was determined using the PLAC test (diaDexus, Inc), and Hcy by recombinant cycling assay (Roche Hitachi 911). Logistic regression was used to predict AD case status. We assayed for Lp‐PLA2 in the brain tissue of cases and controls.ResultsAD case status was independently associated with Lp‐PLA2 and Hcy above the median (odds ratio [OR] = 1.91; 95% confidence interval [CI] = 1.22–2.97; P < .001 and OR = 1.81; 95% CI = 1.16–2.82; P = .009, respectively). Lp‐PLA2, but not Hcy, interacted with CVDE to increase risk. Lp‐PLA2 was absent from the brain tissue in both groups.DiscussionHigher L...

2025, Journal of Internal Medicine

BackgroundComorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic.MethodCohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls.ResultsSARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS‐CoV‐2 positive patients (n = 6937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for i...

2025, Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism

2025, Folia Microbiologica

Our aim was to detect markers of Chlamydia pneumoniae (CPN) and human cytomegalovirus (HCMV) infection in patients with peripheral vascular occlusive disease and to follow markers of inflammation, endothelial dysfunction and lipid metabolism alteration in patients with active infection. CPN genome was detected in 9 (47.4 %) patients by at least one PCR method. Serological markers of acute CPN infection were found in 5 (26.3 %) subjects; each of them showed also positivity in at least one of the PCR methods. HCMV DNA were detected in 2 (10.5 %) patients; HCMV-specific antibodies were detected in 14 (73.7 %) subjects, however only in IgG subclass. Subjects with HCMV PCR positivity thus showed no serological markers of active HCMV infection. Laboratory findings of acute CPN infection were associated with increased plasma levels of Lp(a), triacylglycerols, atherogenic index of plasma and E-selectin (p < 0.05). No significant differences were found in the other markers, including plasma levels of total cholesterol, ferritin, homocysteine, oxidized LDL, IL-6, IL-8, IL-18, TNF-, soluble forms of VCAM-1 and ICAM-1, von Willebrand factor, C-reactive protein, and plasma nitrites & nitrates. Frequent presence of chlamydial DNA in atheromatous plaques from patients with peripheral vascular disease was confirmed. HCMV DNA was detected only sporadically and with positivity in anamnestic anti-HCMV antibodies (IgG) only, indicating a rare presence of latent virus rather than active replication. Patients with laboratory markers of acute CPN infection exhibited more pronounced alterations in lipid metabolism and endothelial dysfunction.

2025, Clinical Reviews in Allergy & Immunology

Atherosclerosis is a disease of the vascular wall, which predominantly affects large and medium-sized arteries. It represents a leading cause of morbidity and mortality in the Western world. In the last few decades, it has been clearly shown that immune system plays a relevant role in atherogenesis. The effectors of both innate and adaptive immunity, including immune cells, cell or soluble receptors, cytokines, chemokines, complement components or coagulation systems, and autoantibodies are able to modulate atherosclerosis. Among proteins belonging to innate immunity, the highly conserved pentraxin family, which encompass C-reactive protein (CRP), serum amyloid P (SAP), and the long pentraxin 3 (PTX3) seems to be directly involved in the induction and progression of atherosclerosis. By immunohistochemical staining, pentraxins were found within the atherosclerotic plaques where they could play a key role interacting with atherogenic-modified lipoproteins, favoring the formation of foam cells, and exerting a proinflammatory action. Pentraxin serum levels have been shown to be associated with clinical and subclinical atherosclerosis in general population. Antibodies against pentraxins have been demonstrated in patients with autoimmune diseases, but their role in atherogenesis is still controversial.

2025, Applied and Environmental Microbiology

Pulsed-field gel electrophoresis of restriction endonuclease-digested genomic DNA from a large collection of clinical isolates of Rhodococcus equi, an important pathogen of foals, was used to compare strain distribution between farms and over time. Forty-four strains were found among 209 isolates, with 5 of these accounting for over half the isolates and the 22 strains isolated more than once accounting for 90% of the isolates. The average genotypic diversity on each farm and in each year was found to be less than the genotypic diversity of the isolates taken as a whole, with 5.2% of the total diversity being due to differences between farms and 5.5% to differences between years. A small number of strains on each farm were found to have caused at least half the clinical cases of disease, and these varied between farms and, to a lesser extent, years. Most strains were found on more than one farm, and some very similar restriction patterns were found among isolates from different continents, indicating that strains can be very widespread. Multiple strains were isolated in five of the six cases in which more than one isolate from a single foal was examined, indicating that disease may commonly be caused by simultaneous infection with multiple strains. It was concluded that there are a number of different strains of R. equi which carry the vapA gene, and these strains tend to be widespread, but individual farms tend to have particular strains associated with them.

2025, Metabolism

In men in the post World War II birth cohort, i.e., men aged 40-49, whites in the United States (U.S.) had significantly higher levels of intima-media thickness of the carotid arteries (IMT) than the Japanese in Japan. The difference remained after adjusting for traditional risk factors. Primary genetic effects are unlikely, given the degree to which IMT is increased in the Japanese who migrated to the U.S. We investigated whether the differences in the distributions of lipoprotein subclasses explain the difference in IMT between the two populations. We examined population-based samples of 466 randomly-selected men aged 40-49 (215 whites from Allegheny County, U.S., and 241 Japanese from Kusatsu, Japan). Lipoprotein subclasses were determined by nuclear magnetic resonance (NMR) spectroscopy. The whites had significantly higher levels of large very-low-densitylipoprotein particles and significantly lower levels of large high-density-lipoprotein particles than the Japanese, whereas the two populations had similar levels of small low-density-lipoprotein particles. The two populations had similar associations of IMT with NMR lipoproteins. Adjusting for NMR lipoproteins did not attenuate the significant difference in IMT between the two populations (0.671 ± 0.006 for the whites and 0.618 ± 0.006 mm for the Japanese, P=0.01, mean (standard error)). Differences in the distributions of NMR lipoproteins between the two populations did not explain the higher IMT in the whites.

2025, European Heart Journal

Background According to previous studies, Familial Combined Hyperlipidemia (FCH) is related to metabolic syndrome. However, it is unclear whether the presence of increased Lipoprotein (a) [Lp (a)] modifies the characteristics of metabolic syndrome in patients with FCH. Thus, the aim of our study was to identify and compare the components of metabolic syndrome in patients with FCH according to their Lp (a) levels. Methods We enrolled 906 patients (592 males, mean age 49±11 years) who fulfilled the FCH criteria, from the outpatient lipid clinic of our hospital.Venous blood samples were obtained for the determination of plasma glucose and lipid profile [i.e., total cholesterol, triglycerides (TG), low and high-lipoprotein cholesterol, (LDL, HDL)], as well as levels of Lp (a). Moreover, information was obtained regarding demographic characteristics and blood pressure (BP) levels. Diagnosis of hypertension was based on BP levels≥140/90 mmHg and metabolic syndrome was defined according to...

2025, Arteriosclerosis and thrombosis

Lipoprotein(a) (Lp[a]), a highly atherogenic lipoprotein particle, is the prominent apolipoproteln B-containing lipoprotein in the hedgehog (Lapland PM et al,J LipidRes 1988^29:1157-1170). In the present work, we studied the consequences of the structural homology between the specific Lp(a) glycoprotein, apoprotein(a), and plasminogen on the generation of plasmin by fibrin-bound tissue-type plasminogen activator. The activation of plasminogen was initiated by adding either native plasma or Lp(a)-free plasma supplemented with the equivalent of 0.25 mg/ml of either purified Lp(a) or albumin to a surface of fibrin prepared on microtitration plates and to which human tissue-type plasminogen activator was specifically bound. With the Lp(a)-free plasma, an increase in the binding and activation of plasminogen as a function of time was observed. In contrast, in the presence of Lp(a) (i.e., native plasma or the reconstituted system), a significant decrease in the binding of plasmin(ogen) (-60%) was obtained. These data indicate that hedgehog Lp(a) interferes with the binding and activation of plasminogen at the fibrin surface and may thereby behave as a factor regulating the extent of fibrin deposition. These results support our previous data indicating that high levels of Lp(a) may have antifibrinolytic effects in humans (Rouy D et al, Arterioscler Thromb 1991;ll:629-638), are in agreement with the observation that Lp(a) is a risk factor for atherosclerotic disease, and provide further support to the view of Lp(a) as a link between atherosclerosis and thrombosis. (Arteriosclerosis and Thrombosis 1992;12:146-154) L ipoprotein(a) (Lp[a]) is a genetically deter- mined lipoprotein particle that contains a f specific apolipoprotein, apoprotein(a) (apo[a]), that is highly homologous to plasminogen, the precursor of the fibrinolytic enzyme plasmin. 1 -3 However, apo(a), unlike plasminogen, is not a substrate for plasminogen activators, and high levels of the Lp(a) particle in human plasma are considered an independent risk factor for atherosclerotic cardiovascular disease. 4 -5 A number of studies have therefore been recently devoted to search for a possible role for Lp(a) in both atherosclerosis and thrombo-From the

2025, Chemistry and Physics of Lipids

Plasminogen activation at the surface of fibrin or of cell membranes is a sophisticated specialized system for localized extracellular proteolysis implicated in a large variety of biological functions (fibrinolysis, cell migration and extracellular matrix degradation). Assembly of plasminogen and/or activators at specific binding sites induces conformational changes that make accessible the scissile peptide bond of plasminogen and exposes the active centre of the tissue-type plasminogen activator. The mechanism of activation by pro-urokinase, a second type of activator that binds to cell membrane but not to fibrin, is far from being understood. It may be able, however, in contrast to urokinase, to specifically activate plasminogen bound to partially degraded fibrin. An extremely low K m and high catalytic rate are characteristic of the process of activation at surfaces. In contrast, activation in liquid phase by tissue-type plasminogen activator proceeds at an extremely low catalytic rate. The initiation and amplification of plasminogen activation depend on specific interactions between the modular constitutive units of these proteins and binding sites present on cell or fibrin surfaces. Thus, the most important mechanism for the acceleration of fibrinolysis and pericellular proteolysis is the unveiling of carboxy-terminal lysine residues on these surfaces, to which plasminogen may bind. Since plasminogen bound to carboxy-terminal lysines of progressively degraded firbrin or membranes is readily transformed into plasmin by fibrin-bound t-PA, this mechanism represents the most important pathway for the acceleration and amplification of fibrinolysis. Alpha-2-antiplasmin, by inhibiting plasmin release from surfaces, regulates the extent and rate of this process but has no effect on fibrin-bound or membrane-bound plasmin. Lipoprotein(a), a particle possessing a plasminogen-like apolipoprotein, apo(a), may interfere with this mechanism by inhibiting the specific binding of plasminogen to lysine residues in membrane or fibrin surfaces.

2025, Journal of cardiovascular and thoracic research

Several meta-analyses have provided support for an association between lipoprotein (a) [Lp (a)] and coronary disease, but the correlation of Lp (a) and other coronary risk factors with severity of coronary artery disease (CAD) are ambiguous. In this case control study, plasma Lp (a) concentration, lipid profile, diabetes, hypertension, smoking were evaluated in 108 patients with and without CAD (Case: 55 and Control: 53) who were admitted at heart center in Shahid Beheshti hospital of Zanjan in 2009. Also patients were classified into two risk groups according to their major risk factors; low risk (with two or few risk factors) and high risk (with three and more risk factors). The collected data was analyzed with using chi square, independent sample t-test, fisher's exact test, Mann-Whitney test, Kruskal Wallis test and Pearson's correlation coefficient. The mean concentration of Lp (a) in the case and control groups were 60±11 mg/dL and 32±3 mg/dL, respectively (P=0.054). 41.8% of the case group and 22.6% of the control group have abnormal level of Lp (a) (≥30 mg/dL) (P=0.03). Mean lipoprotein (a) was also higher in three vessels disease compared control group (46±41 vs. 31±23) and maximum level of lipoprotein (a) in control group was 92 mg/dL and in three vessels disease was 520 mg/dL. Between other cardiac risk factors, diabetes was more frequent in case than control groups (29.1% vs 5.7%) and had a significant relationship with severity of coronary disease (P=0.001). The main findings of this study were that mean Lp(a) levels were higher in the three vessels group compared to control and diabetes had significant relationship with the severity of coronary disease.

2025

2025, Current Biology

Background: Many targets of calcium signaling pathways are activated or inhibited by binding the Ca 2+ -liganded form of calmodulin (Ca 2+ -CaM). Here, we test the hypothesis that local Ca 2+ -CaM-regulated signaling processes can be selectively activated by local intracellular differences in free Ca 2+ -CaM concentration. Results: Energy-transfer confocal microscopy of a fluorescent biosensor was used to measure the difference in the concentration of free Ca 2+ -CaM between nucleus and cytoplasm. Strikingly, short receptor-induced calcium spikes produced transient increases in free Ca 2+ -CaM concentration that were of markedly higher amplitude in the cytosol than in the nucleus. In contrast, prolonged increases in calcium led to equalization of the nuclear and cytosolic free Ca 2+ -CaM concentrations over a period of minutes. Photobleaching recovery and translocation measurements with fluorescently labeled CaM showed that equalization is likely to be the result of a diffusion-mediated net translocation of CaM into the nucleus. The driving force for equalization is a higher Ca 2+ -CaM-buffering capacity in the nucleus compared with the cytosol, as the direction of the free Ca 2+ -CaM concentration gradient and of CaM translocation could be reversed by expressing a Ca 2+ -CaM-binding protein at high concentration in the cytosol. Conclusions: Subcellular differences in the distribution of Ca 2+ -CaM-binding proteins can produce gradients of free Ca 2+ -CaM concentration that result in a net translocation of CaM. This provides a mechanism for dynamically regulating local free Ca 2+ -CaM concentrations, and thus the local activity of Ca 2+ -CaM targets. Free Ca 2+ -CaM signals in the nucleus remain low during brief or low-frequency calcium spikes, whereas high-frequency spikes or persistent increases in calcium cause translocation of CaM from the cytoplasm to the nucleus, resulting in similar concentrations of nuclear and cytosolic free Ca 2+ -CaM.

2025, Trends in Analytical Chemistry

The authors regret that there was an error in the published Table . Wrong literature reference numbers were given in Table making the interpretation of the table very confusing to the reader. Table 2 should be replaced with the following corrected table. Table 2 Human lipoprotein studies with coherent NMR and Ultracentrifugation/HPLC measurements. RM: reference method. RM NMR Samples Data Analysis Ref. Spectrometer Probe Experiment type and temperature Cohort N a Storage temperature and time Sample type and preparation for NMR analysis Preprocessing of NMR data Fractions Subfractions Quantification method

2025, Journal of Leukocyte Biology

Macrophage migration and adhesion are important for the control of mycobacterial infection and are critically dependent on the reorganization of the cytoskeleton. Mycobacteria elicit rapid morphological changes, such as cell spreading, a process relevant to in vivo changes of macrophage shape during extravasation and migration. In this study, we investigated the BCG mycobacteria-induced signaling events leading to macrophage cytoskeletal rearrangements employing specific pharmacological inhibitors to suppress distinct kinase pathways known to be elicited by infection. Viable or lysed mycobacteria, as well as purified cell wall lipoprotein p19, TLR2 agonist, induced RAW264.7 cells to extend actin-rich pseudopods, which impart radial spreading within 3 h, leading later to persistent cell polarization. BCG induced rapid activation of phosphatidylinositol 3-kinase, PI3K, activation that was recruited to the activated TLR2 receptor. TLR2- neutralizing antibody inhibited macrophage spread...

2025, Placenta

Objectives: The Liver X receptors (LXR) alpha and beta and their target genes such as the ATP-binding cassette (ABC) transporters have been shown to be crucially involved in the regulation of cellular cholesterol homeostasis. The aim of this study was to characterize the role of LXR alpha/beta in the human placenta under normal physiological circumstances and in preeclampsia. Study design: We investigated the expression pattern of the LXRs and their target genes in the human placenta during normal pregnancy and in preeclampsia. Placental explants and cell lines were studied under different oxygen levels and pharmacological LXR agonists. Main outcome measures: Gene expressions (Taqman PCR) and protein levels (Western Blot) were combined with immunohistochemistry to analyze the expression of LXR and its target genes. Results: In the human placenta, LXRA and LXRB expression increased during normal pregnancy. This was paralleled by the expression of their prototypical target genes, e.g., the cholesterol transporter ABCA1. Interestingly, early-onset preeclamptic placentae revealed a significant upregulation of ABCA1. Culture of JAr trophoblast cells and human first trimester placental explants under low oxygen lead to increased expression of LXRA and ABCA1 which was further enhanced by the LXR agonist T0901317. Conclusions: LXRA together with ABCA1 are specifically expressed in the human placenta and can be regulated by hypoxia. Deregulation of this system in early preeclampsia might be the result of placental hypoxia and hence might have consequences for maternal-fetal cholesterol transport.

2025, Biophysical Journal

We describe application of the implicit solvation model (see the first paper of this series), to Monte Carlo simulations of several peptides in bilayer-and water-mimetic environments, and in vacuum. The membrane-bound peptides chosen were transmembrane segments A and B of bacteriorhodopsin, the hydrophobic segment of surfactant lipoprotein, and magainin2. Their conformations in membrane-like media are known from the experiments. Also, molecular dynamics study of surfactant lipoprotein with different explicit solvents has been reported (

2025, Tidsskrift for Den norske lægeforening

Lipidklinikken og Nasjonal kompetansetjeneste for familiaer hyperkolesterolemi Avdeling for endokrinologi, sykelig overvekt og forebyggende medisin Oslo universitetssykehus, Aker sykehus Forfatterbidrag: idé, litteratursøk og førsteutkast, utforming, revisjon og godkjenning av manuskriptet. Tone Svilaas er ph.d., spesialist i indremedisin og overlege. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter. Preventiv kardiologi Avdeling for endokrinologi, sykelig overvekt og forebyggende medisin Oslo universitetssykehus, Aker sykehus Forfatterbidrag: faglig innspill og utforming, revisjon og godkjenning av manuskriptet. Tor Ole Klemsdal er ph.d., spesialist i indremedisin og hjertesykdommer, overlege og seksjonsleder. Forfatteren har fylt ut ICMJE-skjemaet og oppgir følgende interessekonflikter: Han har mottatt honorar for foredrag fra AstraZeneca, BMS, Pfizer og Sanofi-Aventis (produsent av PCSK9-hemmeren alirokumab). Han har mottatt honorar fra Helsedirektoratet som ekspert ved utforming av nasjonale retningslinjer. Enhet for hjertegenetikk Avdeling for medisinsk genetikk Oslo universitetssykehus, Ullevål sykehus Høyt nivå av lipoprotein(a) -utredning og behandling | Tidsskrift for Den norske legeforening TONE SVIL A AS TOR OLE KLEMSDAL MARTIN PR ØVEN BOGSRUD Forfatterbidrag: faglig innspill og utforming, revisjon og godkjenning av manuskriptet. Martin Prøven Bogsrud er ph.d., lege, forsker og enhetsleder. Forfatteren har fylt ut ICMJE-skjemaet og oppgir følgende interessekonflikter: Han har mottatt honorar for foredrag og deltagelse i ekspertgruppemøter fra Amgen (produsent av PCSK9-hemmeren evolokumab) og Sanofi (produsent av PCSK9-hemmeren alirokumab). Han er rådgiver for pasientorganisasjonen FH Norge (familiaer hyperkolesterolemi) og leder for referansegruppen for Nasjonal kompetansetjeneste for familiaer hyperkolesterolemi. Vestfold indremedisinske senter, Sandefjord Forfatterbidrag: faglig innspill og utforming, revisjon og godkjenning av manuskriptet. Asgeir Graesdal er spesialist i indremedisin og avtalespesialist. Forfatteren har fylt ut ICMJE-skjemaet og oppgir følgende interessekonflikter: Han har mottatt honorar for møter med allmennleger fra Novartis (produsent av antisense-oligonukleotidet pelacarsen), Sanofi (produsent av PCSK9-hemmeren alirokumab) og Amgen (produsent av PCSK9-hemmeren evolokumab). Klinikk for hjertemedisin St. Olavs hospital og Institutt for sirkulasjon og bildediagnostikk Fakultet for medisin og helsevitenskap NTNU Forfatterbidrag: faglig innspill og utforming, revisjon og godkjenning av manuskriptet. Elisabeth Kleivhaug Vesterbekkmo er spesialist i indremedisin og hjertesykdommer, overlege og doktorgradsstipendiat. Forfatteren har fylt ut ICMJE-skjemaet og oppgir følgende interessekonflikter: Hun har deltatt i ekspertgruppemøter og mottatt honorar for dette og for foredrag fra Amgen (produsent av PCSK9-hemmeren evolokumab), Novartis (produsent av antisense-oligonukleotidet pelacarsen) og Sanofi (produsent av PCSK9-hemmeren alirokumab). Hun er rådgiver for AG Preventiv, Norsk cardiologisk selskap (NCS), Norsk indremedisinsk forening, Nasjonal kompetansetjeneste Trening som medisin og Nasjonal kompetansetjeneste for familiaer hyperkolesterolemi. Avdeling for endokrinologi, sykelig overvekt og forebyggende medisin Oslo universitetssykehus, Aker sykehus Høyt nivå av lipoprotein(a) -utredning og behandling | Tidsskrift for Den norske legeforening

2025, Arteriosclerosis, Thrombosis, and Vascular Biology

E levations in lipoprotein(a) (Lp[a]) represent the most common genetic dyslipidemia worldwide affecting at least 1 in 5 individuals. 1 Lp(a) has been confirmed as a risk factor for myocardial infarction (MI) and aortic stenosis (AS) and 1 in 3 individuals with levels >30 mg/dL are at high cardiovascular risk. Genetic studies, using the Mendelian randomization approach, have also provided strong evidence for causation. Taken together, the evidence suggests that Lp(a) may be a novel therapeutic target for preventing cardiovascular disease. 2 However, the lack of targeted effective treatments for Lp(a) lowering has limited its clinical relevance. Recently, several novel lipid-lowering therapies, including PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors and antisense oligonucleotides, have been developed that can markedly lower Lp(a). With potent Lp(a)-lowering therapies on the horizon, we sought to estimate the potential population impact of Lp(a) lowering that may be achieved by these therapies in primary prevention. Accordingly, we estimated the attributable risk proportion and population attributable risk proportion for MI and aortic valve stenosis if all individuals with high Lp(a) ≥50 mg/dL, a level above which Lp(a) has been shown to be most pathogenic, 9 were treated to normalize their Lp(a) levels to <50 mg/dL. Materials and Methods are available in the online-only Data Supplement.

2025, Molecular Systems Biology

Symbiotic gut microorganisms (microbiome) interact closely with the mammalian host's metabolism and are important determinants of human health. Here, we decipher the complex metabolic effects of microbial manipulation, by comparing germfree mice colonized by a human baby flora (HBF) or a normal flora to conventional mice. We perform parallel microbiological profiling, metabolic profiling by 1 H nuclear magnetic resonance of liver, plasma, urine and ileal flushes, and targeted profiling of bile acids by ultra performance liquid chromatography-mass spectrometry and short-chain fatty acids in cecum by GC-FID. Top-down multivariate analysis of metabolic profiles reveals a significant association of specific metabotypes with the resident microbiome. We derive a transgenomic graph model showing that HBF flora has a remarkably simple microbiome/metabolome correlation network, impacting directly on the host's ability to metabolize lipids: HBF mice present higher ileal concentrations of tauro-conjugated bile acids, reduced plasma levels of lipoproteins but higher hepatic triglyceride content associated with depletion of glutathione. These data indicate that the microbiome modulates absorption, storage and the energy harvest from the diet at the systems level.

2025, Experimental Gerontology

The long-term health benefits of caloric restriction (CR) are well known but the associated molecular mechanisms are poorly understood despite increasing knowledge of transcriptional and related metabolic changes. We report new metabolic insights into long-term CR in nonhuman primates revealed by the holistic inspection of plasma 1 H-NMR spectroscopic metabolic and lipoprotein profiles. The results revealed attenuation of aging-dependant alterations of lipoprotein and energy metabolism by CR, noted by relative increase in HDL and reduction in VLDL levels. Metabonomic analysis also revealed animals exhibiting distinct metabolic trajectories from aging that correlated with higher insulin sensitivity. The plasma profiles of insulin-sensitive animals were marked by higher levels of gluconate and acetate suggesting a CR-modulated increase in metabolic flux through the pentose phosphate pathway. The metabonomic findings, particularly those that parallel improved insulin sensitivity, are consistent with diminished adiposity in CR monkeys despite aging. The metabolic profile and the associated pathways are compatible with our previous findings that CRinduced gene transcriptional changes in tissue suggest the critical regulation of peroxisome proliferator-activated receptors as a key mechanism. The metabolic phenotyping provided in this study can be used to define a reference molecular profile of CR-associated health benefits and longevity in symbiotic superorganisms and man.

2025, Clinica chimica acta; international journal of clinical chemistry

Low-density lipoprotein (LDL) particle (P, or molar) concentration has been shown to be a more sensitive marker of cardiovascular disease (CVD) risk than LDL cholesterol. Although elevated circulating lipoprotein(a) [Lp(a)] cholesterol and mass have been associated with CV risk, no practicable method exists to measure Lp(a)-P. We have developed a method of determining Lp(a)-P suitable for routine clinical use. Lipoprotein immunofixation electrophoresis (Lipo-IFE) involves rigidly controlled electrophoretic separation of serum lipoproteins, probing with polyclonal apolipoprotein B antibodies, then visualization after staining with a nonspecific protein stain (Acid Violet). Lipo-IFE was compared to the Lp(a) mass assay for 1086 randomly selected patient samples, and for 254 samples stratified by apo(a) isoform size. The Lipo-IFE method was shown to be precise (CV <10% above the 50 nmol/l limit of quantitation) and linear across a 16-fold range. Lipo-IFE compared well with the mass-...

2025, Journal of clinical lipidology

The importance of lipoprotein (a)-Lp(a)-as a cardiovascular (CV) risk marker has been underscored by recent findings that CV risk is directly related to baseline Lp(a) levels, even in well-treated patients. Although there is currently little that can be done pharmacologically to lower Lp(a) levels, knowledge of its serum concentration is important in overall risk assessment. This review focuses on 1 aspect of Lp(a) that is rarely discussed directly: how to express its levels in serum. There is considerable confusion on this point, and a fuller understanding of what the concentration units mean will help improve study-to-study comparisons and thereby advance our understanding of the pathobiology of this lipoprotein particle. As discussed here, the term Lp(a) mass refers to the entire mass of the particle: lipids, proteins, and carbohydrates combined. At present, there are no commercially available assays that are completely insensitive to the variability in particle mass, which arise...

2025, The Journal of Clinical Endocrinology & Metabolism

Very little is known about the atherosclerotic risk in patients with childhood-onset growth hormone deficiency (GHD). Such data may be relevant to reconstructing the natural course of the cardiovascular abnormalities associated with GHD. To this end, the intima-media thickness (IMT) of the carotid arteries and the vascular risk factors were evaluated in 14 childhood-onset GHD patients (age 25 Ϯ 1 yr, BMI 22 Ϯ 0.6 Kg/m 2 ) and in 14 age-, sex-, and BMI-matched control subjects. IMT was greater in GHD patients (0.83 Ϯ 0.06 and 0.81 Ϯ 0.06 mmol/L for the right and left carotid artery) than in controls (0.64 Ϯ 0.03 and 0.64 Ϯ 0.04 mmol/L, P Ͻ 0.01 and P Ͻ 0.02, respectively). Serum total and lipoprotein cholesterol, and serum total triglycerides did not differ between the two groups. However, a significant increase in low density lipid triglycerides was present in GHD patients (0.27 Ϯ 0.02 mmol/L) compared with controls (0.19 Ϯ 0.01; P ϭ 0.007). No difference was found in plasma fibrinogen and serum Lp(a) levels. Plasma glucose and insulin concentrations were similar in GHD and control subjects both in the fasted state and after an oral glucose load. In conclusion, young patients with childhood-onset GHD show an increased IMT in the absence of clear-cut abnormalities of the classic vascular risk factors. This suggests a role for GH deficiency per se in increasing the atherosclerotic risk. (

2025, Atherosclerosis

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are unequivocally useful for lowering cholesterol levels in patients with dyslipidemias characterized by elevations in total and/or low-density lipoprotein cholesterol. The beneficial effects of statins to lower serum cholesterol translate into significant reductions in cardiovascular morbidity and mortality. In addition to lowering cholesterol levels, statins have other biological effects relevant to cardiovascular homeostasis including anti-inflammatory actions and downregulation of angiotensin type 1 receptor expression that contribute to improvements in enodthelial function and arterial compliance. Since enodthelial dysfunction and reduced arterial compliance are important pathophysiological determinants of essential hypertension, these actions of statins raise the possibility that statin therapy may be useful for simultaneously treating dyslipidemias and hypertension. However, it has been unclear whether statins are effective in lowering blood pressure. This controversy stems from a variety of methodological limitations including inadequate sample size, confounding effects of antihypertensive drugs, differences in blood pressure measurement techniques, and differences in patient populations. However, based on published results from both small clinical studies and large randomized clinical trials, statins modestly lower blood pressure in patients with high, but not normal, blood pressure, regardless of cholesterol level.

2025, Nature

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for... more