Maureen Sampson - Academia.edu (original) (raw)

Papers by Maureen Sampson

Molecular & Cellular Proteomics, Dec 1, 2015

Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. H... more Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to low density lipoprotein cholesterol (LDL-C) lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n = 10) with normal LDL-C (<130 mg/ dL), who were treated with rosuvastatin (20 mg/day) for 28 days. Proteomic analysis of size-exclusion chromatography isolated LDL, large high density lipoprotein (HDL-L), and small HDL (HDL-S) fractions and spectral counting was used to compare relative protein detection before and after statin therapy. Significant protein changes were found in each lipoprotein pool and included both increases and decreases in several proteins involved in lipoprotein metabolism, complement regulation and acute phase response. The most dramatic effect of the rosuvastatin treatment was an increase in α-1-antirypsin (A1AT) spectral counts associated with HDL-L particles. Quantitative measurement by ELISA confirmed an average 5.7fold increase in HDL-L associated A1AT. Molecular modeling predictions indicated that the hydrophobic reactive center loop of A1AT, the functional domain responsible for its protease inhibitor activity, is likely involved in lipid binding and association with HDL was found to protect A1AT against oxidative inactivation. Cell culture experiments, using J774 macrophages, demonstrated that the association of A1AT with HDL enhances its antiprotease activity, preventing elastase induced production of tumor From the ‡Lipoprotein Metabolism Section,

American Journal of Respiratory and Critical Care Medicine, May 1, 2015

Rationale: Although lipids, apolipoproteins, and lipoprotein particles are important modulators o... more Rationale: Although lipids, apolipoproteins, and lipoprotein particles are important modulators of inflammation, varying relationships exist between these parameters and asthma. Objectives: To determine whether serum lipids and apolipoproteins correlate with the severity of airflow obstruction in subjects with atopy and asthma. Methods: Serum samples were obtained from 154 atopic and nonatopic subjects without asthma, and 159 subjects with atopy and asthma. Serum lipid and lipoprotein levels were quantified using standard diagnostic assays and nuclear magnetic resonance (NMR) spectroscopy. Airflow obstruction was assessed by FEV 1 % predicted. Measurements and Main Results: Serum lipid levels correlated with FEV 1 only in the subjects with atopy and asthma. Serum levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) were positively correlated with FEV 1 in subjects with atopy and asthma, whereas a negative correlation existed between FEV 1 and serum levels of triglycerides, low-density lipoprotein (LDL) cholesterol, apolipoprotein B (apoB), and the apoB/apoA-I ratio. NMR spectroscopy identified a positive correlation between FEV 1 and HDL NMR particle size, as well as the concentrations of large HDL NMR particles and total IDL NMR (intermediate-density lipoprotein) particles in subjects with atopy and asthma. In contrast, LDL NMR particle size and concentrations of LDL NMR and VLDL NMR (very-low-density lipoprotein) particles were negatively correlated with FEV 1 in subjects with atopy and asthma. Conclusions: In subjects with atopy and asthma, serum levels of apoA-I and large HDL NMR particles are positively correlated with FEV 1 , whereas serum triglycerides, LDL cholesterol, and apoB are associated with more severe airflow obstruction. These results may facilitate future studies to assess whether apoA-I and large HDL NMR particles can reduce airflow obstruction and disease severity in asthma.

Pediatric Research, May 21, 2019

BACKGROUND: Cardiovascular (CV) complications are the most significant cause of mortality in adul... more BACKGROUND: Cardiovascular (CV) complications are the most significant cause of mortality in adults with Cushing disease (CD); little is known about CV risk factors in children with CD. Measurement of lipoprotein particles by nuclear magnetic resonance (NMR) spectroscopy is a novel technology to assess CV risk. The objective of the current study is to analyze the NMR lipid profile in pediatric CD patients before and 1 year after remission. METHODS: NMR lipid profile was obtained via the Vantera NMR analyzer, using frozen serum samples from 33 CD patients (mean age 13.8 ± 4.0 years) evaluated between 1997 and 2017 at the National Institutes of Health (NIH) Clinical Center (CC). RESULTS: GlycA (glycosylated acute-phase proteins), triglyceride-rich particles (TRLP medium and very small sizes), low-density lipoprotein (LDL) particles (LDLP total and large size), high-density lipoprotein (HDL) particles (HDLP total, medium and small sizes), total cholesterol, LDL-cholesterol, HDL-cholesterol, GlycA inflammatory biomarker, and apolipoprotein B and apolipoprotein A1 (ApoA1) concentrations showed statistically significant changes after remission of CD (p < 0.05). CONCLUSION: In our study population, most of the lipid variables improved post-CD remission, with the exception of HDL and ApoA1, indicating that NMR lipoprotein profile may be a helpful tool in assessing the CV risk in pediatric patients with CD.

Clinical Chemistry, Jun 1, 2000

Serum lipoprotein analysis frequently is used in assessing the risk for coronary artery disease a... more Serum lipoprotein analysis frequently is used in assessing the risk for coronary artery disease and for monitoring cholesterol-lowering therapy (1)(2). A recent improvement in the analysis of lipoproteins is the development of homogeneous assays for HDL-cholesterol (HDL-C) (3)(4) that are easier to perform because they do not require the physical separation of the apolipoprotein B (apoB)-containing lipoproteins by precipitation and centrifugation. The measurement of LDL-cholesterol (LDL-C) and apoB, the principal protein on LDL, is also useful for estimating the risk for cardiovascular risk (1)(2). An isolated increase in apoB in the absence of increased total cholesterol and LDL-C is diagnostic for a risk condition called hyperapoB-lipoproteinemia (5). We describe a simple modification of an antibody-based commercial homogeneous assay for HDL-C (EZ-HDL; Sigma Diagnostics) that in addition to measuring HDL-C, also provides an estimate of the apoB concentration. In step 1 of the EZ-HDL assay, an anti-apoB antibody is added, which binds to the surface of the apoB-containing …

JCI insight, Apr 7, 2022

Conflict of interest: NNM is a fulltime US government employee and has served as a consultant for... more Conflict of interest: NNM is a fulltime US government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, AstraZeneca, Janssen Pharmaceuticals, Inc, Novartis, and Abcentra receiving grants and/or research funding; and as a principal investigator for the NIH receiving grants and/or research funding. ATR is a full-time US government employee and serves as a principal investigator for the NIH receiving grants and/or research funding.

Journal of Lipid Research, Aug 1, 2017

A type 2 high asthma endotype has been identified that is characterized by airway and systemic eo... more A type 2 high asthma endotype has been identified that is characterized by airway and systemic eosinophilic inflammation (1-3). Biomarkers to define type 2 high asthma include blood eosinophil counts and serum periostin levels. Blood eosinophil counts correlate with disease severity in eosinophil-predominant asthma and predict responsiveness to treatment with anti-interleukin (IL)-5 monoclonal antibodies (4-17). Increased serum levels of periostin, which can be induced by IL-13 in airway epithelial cells (18-20), have also been used to identify type 2 high asthmatics for subgroup analysis in clinical trials of anti-IL-13 monoclonal antibody therapy (21-24). There is an increasing recognition that apolipoprotein pathways may participate in the pathogenesis of lung disease (25). Both apoE and apoA-I mimetic peptides have been shown to suppress type 2 inflammation in murine models of allergen-induced airway disease (26-28). Endothelial lipase, which is a phospholipase that hydrolyzes phospholipids and promotes the catabolism of HDL particles, is expressed in the lung where it may modulate eosinophilic inflammation. Consistent with this, allergen-challenged endothelial lipase knockout mice have high serum HDL levels and decreased eosinophilic lung inflammation (29). Among obese adolescent asthmatics, serum HDL levels have been inversely correlated with monocyte activation and numbers of patrolling monocytes (30). We have also recently shown that serum levels of HDL cholesterol (HDL-C), large HDL particles measured by NMR spectroscopy (HDL NMR particles), and apoA-I are positively associated with forced expiratory volume in 1 s (FEV 1) in atopic Abstract Blood eosinophil counts and serum periostin levels are biomarkers of type 2 inflammation. Although serum levels of HDL and apoA-I have been associated with less severe airflow obstruction in asthma, it is not known whether serum lipids or lipoprotein particles are correlated with type 2 inflammation in asthmatics. Here, we assessed whether serum lipids and lipoproteins correlated with blood eosinophil counts or serum periostin levels in 165 atopic asthmatics and 163 nonasthmatic subjects with and without atopy. Serum lipids and lipoproteins were quantified using standard laboratory assays and NMR spectroscopy. Absolute blood eosinophils were quantified by complete blood counts. Periostin levels were measured using the Elecsys® periostin assay. In atopic asthmatics, blood eosinophils negatively correlated with serum HDL cholesterol and total HDL particles measured by NMR spectroscopy (HDL NMR). Serum periostin levels negatively correlated with total HDL NMR. In contrast, blood eosinophil counts positively correlated with serum triglyceride levels. This study demonstrates for the first time that HDL particles were negatively correlated, whereas serum triglycerides were positively correlated, with blood eosinophils in atopic asthmatics. This supports the concept that serum levels of HDL and triglycerides may be linked to systemic type 2 inflammation in atopic asthma.-Barochia, A

Clinical Chemistry, Oct 1, 1997

Nutrients, Mar 12, 2020

Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both shared and diffe... more Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both shared and different cardiovascular effects, and commonly used fish oil supplements have considerably varied EPA/DHA ratios. Aims: We compared the effects of fish oil supplements with different EPA/DHA ratios on lipoprotein metabolism. Methods: In a double-blind, randomized cross-over study, normolipidemic adults (n = 30) consumed 12 g/day of EPA-rich (EPA/DHA: 2.3) or DHA-rich (EPA/DHA: 0.3) fish oil for 8-weeks, separated by an 8-week washout period. Results: Both fish oil supplements similarly lowered plasma TG levels and TG-related NMR parameters versus baseline (p < 0.05). There were no changes in plasma cholesterol-related parameters due to either fish oil, although on-treatment levels for LDL particle number were slightly higher for DHA-rich oil compared with EPA-rich oil (p < 0.05). Both fish oil supplements similarly altered HDL subclass profile and proteome, and down regulated HDL proteins related to inflammation, with EPA-rich oil to a greater extent. Furthermore, EPA-rich oil increased apoM abundance versus DHA-rich oil (p < 0.05). Conclusions: Overall, fish oil supplements with varied EPA/DHA ratios had similar effects on total lipids/lipoproteins, but differences were observed in lipoprotein subfraction composition and distribution, which could impact on the use of EPA versus DHA for improving cardiovascular health.

AIDS Research and Human Retroviruses, May 1, 2016

Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-den... more Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCVmonoinfected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV-coinfected subjects. No change in serum LDL-C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV-coinfected subjects.

Biomedical Chromatography, Oct 5, 2012

Linoleic acid (LA) and LA-esters are the precursors of LA hydroperoxides, which are readily conve... more Linoleic acid (LA) and LA-esters are the precursors of LA hydroperoxides, which are readily converted to 9-and 13-hydroxy-octadecadienoic acid (HODE) and 9-and 13-oxo-octadecadienoic acid (oxo ODE) metabolites in vivo. These four oxidized LA metabolites (OXLAMs) have been implicated in a variety of pathological conditions. Therefore, their accurate measurement may provide mechanistic insights into disease pathogenesis. Here we present a novel quadrupole timeof-flight mass spectrometry (Q-TOFMS) method for quantitation and identification of target OXLAMs in rat plasma. In this method, the esterified OXLAMs were base-hydrolyzed and followed by liquid-liquid extraction. Quantitative analyses were based on one-point standard addition with isotope dilution. The target metabolites were quantified by multiple reaction monitoring (MRM) extracted ion chromatograms generated post-acquisition with 10 ppm extraction window. The limit of quantitation was 9.7-35.9 nmol/L depending on the metabolite. The method was reproducible with coefficient of variation below 18.5%. Mean concentrations of target metabolites were 57.8, 123.2, 218.1, and 57.8 nmol/L for 9-HODE, 13-HODE, 9-oxoODE, and 13-oxoODE, respectively. Plasma levels of total OXLAMs were 456.9 nmol/L, which correlated well with published concentrations obtained by gas chromatography/mass spectrometry (GC/MS). The concentrations were also obtained utilizing a standard addition curve approach. The calibration curves were linear with correlation coefficients > 0.991. Concentrations of 9-HODE, 13-HODE, 9-oxoODE, and 13-oxoODE were 84.0, 138.6, 263.0, and 69.5 nmol/L, respectively, which were consistent with the results obtained from one-point standard addition. Target metabolites were simultaneously characterized based on accurate Q-TOFMS data. This is the first study of secondary LA metabolites using Q-TOFMS.

Circulation, Feb 28, 2023

Introduction: Over 6 million people in the U.S. have heart failure (HF), less than half are expec... more Introduction: Over 6 million people in the U.S. have heart failure (HF), less than half are expected to survive beyond 5 years. The need to better stratify mortality risk in HF is recognized. Frailty is associated with mortality in HF but not routinely measured clinically. As frailty is linked to inflammation and malnutrition, we hypothesized that the Metabolic Vulnerability Index (MVX) a multimarker score of systemic inflammation (small HDL particles, GlycA) and malnutrition (leucine, valine, isoleucine, citrate), could serve as a biomarker of frailty to predict mortality risk. Methods: Clinical data and plasma were collected from 1,389 patients from a HF community cohort between 2003-2012. We measured frailty using the Rockwood Index as the proportion of deficits present out of 32 physical limitations and comorbidities. MVX was calculated from the nuclear magnetic resonance LipoProfile® test. Patients were categorized by frailty (0-0.15; 0.16-0.27; 0.28-0.78) and MVX (33.4-50, 50-60, 60-70, 70-85.8) cutpoints. Cox models estimated the association of frailty and MVX assignment with mortality, adjusted for Meta-Analysis Global Group in Chronic HF (MAGGIC) score, a validated clinical risk score for HF mortality. Results: Frailty and MVX scores were available in 985 patients (median age 77, IQR: 67-84; 48% women). Higher frailty was associated with higher MVX (p-trend < 0.001). The highest frailty and MVX groups experienced large increases in risk of death, after adjustment for MAGGIC score (HR=3.3, 95% CI=2.6-4.2) and (HR=2.7, 95% CI=2.1-3.5), respectively. When adjusted for one another and MAGGIC score, MVX and frailty associations with death were only minimally attenuated: frailty (HR=3.2, 95% CI=2.5-4.0) and MVX (HR=2.4, 95% CI=1.9-3.2) (Figure 1). Conclusion: In this community cohort of patients with HF, frailty and MVX are positively associated with one another. However, both indicators are independently associated with an increased risk of death and can contribute to risk stratification.

Clinical Biochemistry, Aug 1, 2000

Clinical Chemistry, Feb 1, 1994

We compared the effects of specimen turbidity and glycerol concentration on nine enzymatic method... more We compared the effects of specimen turbidity and glycerol concentration on nine enzymatic methods for triglyceride measurement. We assayed 51 specimens with triglyceride concentrations of 0.85-8.21 mmol/L (75-727 mg/dL) and turbidity at 420 nm equivalent to > or = 0.1 mmol/L (8.8 mg/dL) triglyceride (measured as part of our comparison method). The data were analyzed by multiple regression, which gave coefficients for the effects of glycerol concentration and the change in turbidity during the reaction. The effects of specimen turbidity and glycerol concentration were method-dependent and ranged from 6.20% to -15.67% of the measured result. The magnitude of the turbidity effect (in assays with a significant turbidity interference) was similar to that for glycerol (in assays with a significant glycerol interference). A triglyceride assay with a bichromatic measurement was less subject to interference from turbidity.

Diabetes, Jun 1, 2022

Heart failure (HF) is associated with metabolic alterations, including insulin resistance (IR) . ... more Heart failure (HF) is associated with metabolic alterations, including insulin resistance (IR) . Perturbations in lipid metabolism and insulin signaling may impact outcomes, but the relationship between IR and mortality is not well characterized. The Lipoprotein Insulin Resistance Index (LPIR) is a score (0-100; higher values signify greater IR) calculated from 6 lipoprotein subclass/size parameters measured by nuclear magnetic resonance (NMR) . We examined the association between LPIR and death in a HF community cohort. LPIR was measured by NMR LipoProfile®. Meta-Analysis Global Group in Chronic HF (MAGGIC) scores were calculated from clinical data. Kaplan-Meier curves were used to evaluate survival; Cox regression was used to estimate risk of death by LPIR quartile. Among 1,381 community-dwelling persons with HF, the median LPIR score was 38 (IQR 21-56) . Higher LPIR was associated with younger age, diabetes, smoking, obesity, and lower MAGGIC scores, but not ejection fraction. Survival increased by LPIR quartile (p<0.001) and at 5 years was 36% [95% CI 31-42], 42% [95% CI 38-48], 51% [95% CI 46-56], and 65% [95% CI 60-70] for quartile 1-4, respectively. The association between LPIR and death was independent of MAGGIC score (Figure) . Higher LPIR was associated with better survival in HF, independently of a validated clinical risk score. More research is needed to examine this paradoxically protective association. Disclosure S. Turecamo: None. A. Wolska: None. J.D. Otvos: Employee; LabCorp. K. Conners: None. S.J. Bielinski: Consultant; Novartis Pharmaceuticals Corporation. J. St Sauver: Research Support; Exact Sciences. V.L. Roger: None. Funding Research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) at National Institutes of Health and by the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, and the Colgate-Palmolive Company.

American Journal of Clinical Pathology

Cholestatic liver diseases, such as primary sclerosing cholangitis and primary biliary cirrhosis,... more Cholestatic liver diseases, such as primary sclerosing cholangitis and primary biliary cirrhosis, can lead to serum accumulation of lipoprotein X (LpX). LpX is a multilamellar particle high in cholesterol but lacking structural apolipoproteins A1 or B. The absence of ApoB results in no negative feedback on cholesterol biosynthesis and prevents LpX clearance from the liver. While clinical signs and symptoms typically precede laboratory findings, it is possible that in medically complex patients the identification of LpX could be the first observation of cholestatic liver disease. Traditional laboratory methods are insufficient to identify LpX as it is of similar density to low-density lipoprotein (LDL). LpX contains a high concentration of cholesterol which is erroneously reported as LDL-C by routine clinical methods. As LpX is a rare complication of liver disease, clinicians may presume the elevation is a coincidental familial hypercholesterolemia rather than a sequela of liver dise...

Journal of Clinical Lipidology, 2020

BACKGROUND: Fish oil enriched in omega-11 long-chain monounsaturated fatty acids (LCMUFAs; C20:1 ... more BACKGROUND: Fish oil enriched in omega-11 long-chain monounsaturated fatty acids (LCMUFAs; C20:1 and C22:1 isomers combined) have shown lipid-lowering and atheroprotective effects in animal models. OBJECTIVE: To perform a first-inhuman trial of LCMUFA-rich saury fish oil supplementation to test its safety and possible effect on plasma lipids. METHODS: A double-blind, randomized, crossover clinical trial was carried out in 30 healthy normolipidemic adults (BMI ,25 kg/m 2 ; mean TG, 84 mg/dL). Treatment periods of 8 weeks were separated by an 8week washout period. Subjects were randomized to receive either 12 g of saury oil (3.5 g of LCMUFA and 3.4 g of omega-3 FAs) or identical capsules with control oil (a mixture of sardine and olive oil; 4.9 g of shorter-chain MUFA oleate and 3 g of omega-3 FAs). RESULTS: Saury oil supplementation was safe and resulted in LDL particle counts 12% lower than control oil (P ,.001). Saury oil also had a minor effect on increasing HDL particle size (9.8 nm vs 9.7 nm; P ,.05) based on a linear mixed effect model. In contrast, control oil, but not saury oil, increased LDL-C by 7.5% compared with baseline (P , .05). Saury oil had similar effects compared with control oil on lowering plasma TG levels, VLDL, and TG-rich lipoprotein particle counts (by w16%, 25%, and 35%, respectively; P ,.05), and increasing HDL-C and cholesterol efflux capacity (by w6% and 8%, respectively; P , .05) compared with baseline. CONCLUSION: Saury oil supplementation is well tolerated and has beneficial effects on several cardiovascular parameters, such as LDL particle counts, HDL particle size, and plasma TG levels. Published by Elsevier Inc. on behalf of National Lipid Association.

Journal of Pharmacology and Experimental Therapeutics, Jun 15, 2016

Niemann-Pick type C (NPC) 1 disease is a rare, inherited, neurodegenerative disease. Clear eviden... more Niemann-Pick type C (NPC) 1 disease is a rare, inherited, neurodegenerative disease. Clear evidence of the therapeutic efficacy of 2-hydroxypropyl-b-cyclodextrin (HPbCD) in animal models resulted in the initiation of a phase I/IIa clinical trial in 2013 and a phase IIb/III trial in 2015. With clinical trials ongoing, validation of a biomarker to track disease progression and serve as a supporting outcome measure of therapeutic efficacy has become compulsory. In this study, we evaluated calcium-binding protein calbindin D-28K (calbindin) concentrations in the cerebrospinal fluid (CSF) as a biomarker of NPC1 disease. In the naturally occurring feline model, CSF calbindin was significantly elevated at 3 weeks of age, prior to the onset of cerebellar dysfunction, and steadily increased to .10-fold over normal at end-stage disease. Biweekly intrathecal administration of HPbCD initiated prior to the onset of neurologic dysfunction completely normalized CSF calbindin in NPC1 cats at all time points analyzed when followed up to 78 weeks of age. Initiation of HPbCD after the onset of clinical signs (16 weeks of age) resulted in a delayed reduction of calbindin levels in the CSF. Evaluation of CSF from patients with NPC1 revealed that calbindin concentrations were significantly elevated compared with CSF samples collected from unaffected patients. Off-label treatment of patients with NPC1 with miglustat, an inhibitor of glycosphingolipid biosynthesis, significantly decreased CSF calbindin compared with pretreatment concentrations. These data suggest that the CSF calbindin concentration is a sensitive biomarker of NPC1 disease that could be instrumental as an outcome measure of therapeutic efficacy in ongoing clinical trials.