Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease
| العنوان: | Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease |
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| المؤلفون: | William F. Hancock-Cerutti, Daniel J. Rader, John S. Millar, Silvia Valentini, Jeffrey T. Billheimer, Marina Cuchel, Jason J. Liu |
| المصدر: | Molecules Volume 26 Issue 22 Molecules, Vol 26, Iss 6862, p 6862 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Apolipoprotein B, Pharmaceutical Science, Organic chemistry, Article, Analytical Chemistry, Coronary artery disease, Basal (phylogenetics), chemistry.chemical_compound, QD241-441, In vivo, Internal medicine, Drug Discovery, medicine, Humans, Physical and Theoretical Chemistry, Aged, lipoprotein metabolism, biology, Apolipoprotein A-I, Chemistry, Cholesterol, Cholesterol, HDL, nutritional and metabolic diseases, Middle Aged, hyperalphalipoprotenemia, medicine.disease, Lipids, Endocrinology, Chemistry (miscellaneous), biology.protein, Cholesteryl ester, Molecular Medicine, Female, lipids (amino acids, peptides, and proteins), Efflux, Lipoproteins, HDL, Ex vivo, cholesterol efflux, coronary artery disease |
| الوصف: | High-density lipoprotein cholesterol (HDL-C) is thought to be atheroprotective yet some patients with elevated HDL-C levels develop cardiovascular disease, possibly due to the presence of dysfunctional HDL. We aimed to assess the metabolic fate of circulating HDL particles in patients with high HDL-C with and without coronary artery disease (CAD) using in vivo dual labeling of its cholesterol and protein moieties. We measured HDL apolipoprotein (apo) A-I, apoA-II, free cholesterol (FC), and cholesteryl ester (CE) kinetics using stable isotope-labeled tracers (D3-leucine and 13C2-acetate) as well as ex vivo cholesterol efflux to HDL in subjects with (n = 6) and without (n = 6) CAD that had HDL-C levels > 90th percentile. Healthy controls with HDL-C within the normal range (n = 6) who underwent the same procedures were used as the reference. Subjects with high HDL-C with and without CAD had similar plasma lipid levels and similar apoA-I, apoA-II, HDL FC, and CE pool sizes with no significant differences in fractional clearance rates (FCRs) or production rates (PRs) of these components between groups. Subjects with high HDL-C with and without CAD also had similar basal and cAMP-stimulated ex vivo cholesterol efflux to HDL. When all subjects were considered (n = 18), unstimulated non-ABCA1-mediated efflux (but not ABCA1-specific efflux) was correlated positively with apoA-I production (r = 0.552, p = 0.017) and HDL FC and CE pool sizes, and negatively with the fractional clearance rate of FC (r = −0.759, p = 4.1 × 10−4) and CE (r = −0.652, p = 4.57 × 10−3). Our data are consistent with the concept that ex vivo non-ABCA1 efflux capacity may correlate with slower in vivo turnover of HDL cholesterol moieties. The use of a dual labeling protocol provided for the first time the opportunity to assess the association of ex vivo cholesterol efflux capacity with in vivo HDL cholesterol metabolic parameters. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1420-3049 |
| DOI: | 10.3390/molecules26226862 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::706ccc59bb983e59a1430e517e648eb4Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....706ccc59bb983e59a1430e517e648eb4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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| DOI: | 10.3390/molecules26226862 |