Effects of dietary cholesterol and palmitic acid on plasma lipoproteins (original) (raw)
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6 The Role of Platelet Surface Ultralarge Complexes in Heparin Induced Thrombocytopenia
2005
Case Western Reserve Univ, Cleveland, OH Multiple genetic factors contribute to the development of cardiovascular diseases (CVD). The objective of this study was to evaluate leukocyte recruitment in mouse models susceptible or resistant to CVD. Peritoneal leukocyte recruitment was evaluated in C57BL/6J (B6) mice, susceptible to atherosclerosis, and A/J mice, mice, resistant to atherosclerosis, using two inflammatory stimuli, a biopolymer implant and a thioglycollate injection. The number of responding neutrophil and monocyte/macrophage cells were quantified (number of cells x 10 6 , mean Ϯ SEM, n ϭ number of mice). Marked differences were found between the two strains. Peritoneal macrophage recruitment induced by the implants, was slightly higher (p Ͻ 0.05) in the A/J (9.8 Ϯ 0.4, n ϭ 8) mice compared to B6 (7.7 Ϯ 0.4, n ϭ 38) mice, but 6h after thioglycollate injection, recruitment of both neutrophils (A/J ϭ 0.6 Ϯ 0.2, n ϭ 8, B6 ϭ 1.9 Ϯ 0.3, n ϭ 16) and macrophages (A/J ϭ 1.9 Ϯ 0.3, n ϭ 8, B6 ϭ 4.7 Ϯ 0.7, n ϭ 16) was 3-fold lower (P Ͻ 0.02) in A/J mice than for B6 mice. At the peak macrophage recruitment time of 72h, macrophage number was also decreased (P Ͻ 0.001) in the A/J mice compared to B6 mice (A/J ϭ 4.9 Ϯ 0.8, n ϭ 8, B6 ϭ 12.8 Ϯ 1.2, n ϭ 22). To dissect the molecular basis for these differences, chromosome substitution strains (CSS), B6 strains of mice with individual A/J chromosomes, one strain for each chromosome, were evaluated for macrophage recruitment 72h after thioglycollate injection. One strain, B6.A10 (7.6 Ϯ 1.3, n ϭ 8), has been identified which carries the trait for decreased (P Ͻ 0.05) macrophage recruitment, similar to the parent A/J strain. Five CSS strains, B6.A5, B6.A8. B6.A14, B6.A15, and B6.AX had significantly (P Ͻ 0.05) increased macrophage recruitment. In the B6.AX strain, macrophage number was nearly 2-fold higher than for B6 mice. Thus, at least one gene or quantitative trait locus on each of the identified chromosomes contributes to macrophage recruitment in the peritoneal thioglycollate inflammatory model and will be evaluated for susceptibility to atherosclerosis. The CSS will ultimately allow us to identify genes that contribute to CVD. Clinic Foundation, Cleveland, OH High-throughput genomic technology identified an unanticipated association between a particular single nucleotide polymorphism (SNP) in the thrombospondin-4 (TSP-4) gene and myocardial infarction. The disease-associated SNP, a proline at position 387 (P387) as compared to the predominant alanine (A387), is associated with an increased risk of MI (adjusted odds ratio: 1.89 Pϭ0.002) and occurs at high frequency within the Caucasian population. Little is known about the TSP-4 gene product and its functions in vivo. In view of the inflammatory hypothesis of atherosclerosis, which invokes prominent roles for leukocytes and cytokines in pathogenesis, the interactions of the TSP-4 variants with human neutrophils (PMN) were investigated. Adhesion of PMA-stimulated PMNs to the recombinant TSP-4 variants was equal and ␣ M  2 -dependent as it was blocked by function blocking mAbs to this integrin and its high affinity ligand NIF (Neutrophil Inhibitory Factor). Involvement of ␣ M  2 in TSP-4 recognition was corroborated using HEK 293 cells overexpressing this integrin. More importantly, despite equal adhesion of PMNs to both TSP-4 variants, PMNs adherent to the P387 TSP-4 were significantly more spread, showed higher expression and robustly more ␣ M  2 clusters on their surface than the cells adherent to the A387 variant. In signaling experiments, the P387 variant induced a substantially more robust tyrosine phosphorylation of 48 -55, 36 -42 and 28 -30 kDa proteins than the A387 variant. The P387 TSP-4 stimulated activation of stress-related MAPKs (Mitogen-activated Protein Kinases): p38 MAPK and SAPK/JNK (Stress-activated Protein Kinase/ c-Jun NH2-terminal Kinase) and also enhanced STAT1 and HSP27 (Heat Shock Protein 27) phosphorylation. In addition, PMNs adherent to TSP-4 (P387) released 4-fold more H 2 O 2 and secreted 2-fold more IL-8 as compared to the A387. The p38 MAPK activation was crucial for H 2 O 2 release since this response was suppressed by a specific p38 inhibitor. PMN adhesion, H 2 O 2 release and p38 MAPK activation were ␣ M  2 integrindependent as they were totally inhibited by ␣ M  2 blockade. Thus, ␣ M  2 plays a central role in proinflammatory activities of the TSP-4 (P387) variant more likely as a consequence of its distinct clustering and activation.
7. Metabolic syndrome in adolescents: role of cholesterol sources, eggs, and others
Handbook of eggs in human function, 2015
Metabolic syndrome (MetS) in adults and now adolescents identifies patients in need of intensive intervention to prevent cardiovascular disease (CVD), type 2 diabetes mellitus, and other chronic diseases. It is based upon the presence of three of five criteria: elevated blood pressure, glucose tolerance, low high-density lipoprotein-cholesterol (HDL-C), high triglycerides, and abdominal obesity. Hormones, etc., from adipocytes, especially from visceral adipose tissue, and/or hyperinsulinemia are considered responsible for MetS and eventually chronic disease. MetS is increasing in adolescents in whom cardiac abnormalities have been noted. Treatment of MetS in adults and adolescents involves reducing fat mass/weight in obese people and dietary changes for each aspect of MetS. In the 1970's dietary recommendations for prevention of CVD were based on misinterpretation of data from epidemiologic studies and animal studies where lipid metabolism differs greatly from humans. Eggs with a high cholesterol and low saturated fat content allow evaluation of the effect of diet on blood cholesterol. Results indicate clearly that dietary cholesterol does not increase low-density lipoprotein-cholesterol but increases HDL-C except in diabetics and cholesterol hyperresponders. This has been known for more than a decade, but dietary guidance for CVD continues to encourage restriction of dietary cholesterol and thus eggs. The positive effect of eggs on blood lipids is accompanied by the best quality protein in our food supply and antioxidants essential for health of the macula of the eye and avoidance of cataracts, i.e. highly bioavailable lutein and zeaxanthin. Milk also provides complete proteins and is the source of the most bioavailable calcium plus vitamin D that is being revealed as vital throughout the body. Milk includes more bioactive peptides than any other common protein food in the diet of the US. Healthful effects of many of them have been identified. Eggs and milk can be powerful allies in management of MetS.
Atherosclerosis, 1998
Studies have shown contrasting results concerning the relation between carotid intima-media thickness (IMT) and apolipoprotein E (apo E) and angiotensin-converting enzyme (ACE) polymorphisms. Subjects, 76 men and 74 women, between 33 and 50 years, without any history of cardiovascular disease and without any anti-hypertensive or lipid lowering medication were selected from the Stanislas cohort. The IMT of carotid and femoral arteries were investigated by B-mode ultrasonography. The common apo E, (C/G) 447 lipoprotein lipase (LPL) and I/D ACE gene polymorphisms and serum ACE activity were determined. In the overall sample, male sex, age, systolic blood pressure, BMI, serum apo B level and tobacco consumption were positively correlated with carotid and femoral IMT. The common apo E polymorphism, the (C/G)LPL 447 polymorphism and ACE activity were not related to carotid and femoral IMT variability in either men or women. Unexpectedly, the I allele of the ACE gene was related to higher femoral IMT than the D allele in non-smokers only. Similar results were observed after adjustment for the main covariates of IMT variability. In conclusion, amongst our young adult sample the candidate risk factors for cardiovascular disease, apo m4, C 447 -LPL and D-ACE alleles and ACE activity were not associated with increased carotid and femoral IMT.