Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease

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-...

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Autores principales:	William Hancock-Cerutti, John S. Millar, Silvia Valentini, Jason Liu, Jeffrey T. Billheimer, Daniel J. Rader, Marina Cuchel
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hyperalphalipoprotenemia lipoprotein metabolism cholesterol efflux coronary artery disease Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/f66898c6d66140b4838705aadba64154
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spelling	oai:doaj.org-article:f66898c6d66140b4838705aadba641542021-11-25T18:27:54ZAssessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease10.3390/molecules262268621420-3049https://doaj.org/article/f66898c6d66140b4838705aadba641542021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6862https://doaj.org/toc/1420-3049High-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 (D<sub>3</sub>-leucine and <sup>13</sup>C<sub>2</sub>-acetate) as well as ex vivo cholesterol efflux to HDL in subjects with (<i>n</i> = 6) and without (<i>n</i> = 6) CAD that had HDL-C levels >90th percentile. Healthy controls with HDL-C within the normal range (<i>n</i> = 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 (<i>n</i> = 18), unstimulated non-ABCA1-mediated efflux (but not ABCA1-specific efflux) was correlated positively with apoA-I production (r = 0.552, <i>p</i> = 0.017) and HDL FC and CE pool sizes, and negatively with the fractional clearance rate of FC (r = −0.759, <i>p</i> = 4.1 × 10<sup>−4</sup>) and CE (r = −0.652, <i>p</i> = 4.57 × 10<sup>−3</sup>). 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.William Hancock-CeruttiJohn S. MillarSilvia ValentiniJason LiuJeffrey T. BillheimerDaniel J. RaderMarina CuchelMDPI AGarticlehyperalphalipoprotenemialipoprotein metabolismcholesterol effluxcoronary artery diseaseOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6862, p 6862 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hyperalphalipoprotenemia lipoprotein metabolism cholesterol efflux coronary artery disease Organic chemistry QD241-441
spellingShingle	hyperalphalipoprotenemia lipoprotein metabolism cholesterol efflux coronary artery disease Organic chemistry QD241-441 William Hancock-Cerutti John S. Millar Silvia Valentini Jason Liu Jeffrey T. Billheimer Daniel J. Rader Marina Cuchel Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease
description	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 (D<sub>3</sub>-leucine and <sup>13</sup>C<sub>2</sub>-acetate) as well as ex vivo cholesterol efflux to HDL in subjects with (<i>n</i> = 6) and without (<i>n</i> = 6) CAD that had HDL-C levels >90th percentile. Healthy controls with HDL-C within the normal range (<i>n</i> = 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 (<i>n</i> = 18), unstimulated non-ABCA1-mediated efflux (but not ABCA1-specific efflux) was correlated positively with apoA-I production (r = 0.552, <i>p</i> = 0.017) and HDL FC and CE pool sizes, and negatively with the fractional clearance rate of FC (r = −0.759, <i>p</i> = 4.1 × 10<sup>−4</sup>) and CE (r = −0.652, <i>p</i> = 4.57 × 10<sup>−3</sup>). 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.
format	article
author	William Hancock-Cerutti John S. Millar Silvia Valentini Jason Liu Jeffrey T. Billheimer Daniel J. Rader Marina Cuchel
author_facet	William Hancock-Cerutti John S. Millar Silvia Valentini Jason Liu Jeffrey T. Billheimer Daniel J. Rader Marina Cuchel
author_sort	William Hancock-Cerutti
title	Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease
title_short	Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease
title_full	Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease
title_fullStr	Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease
title_full_unstemmed	Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease
title_sort	assessing hdl metabolism in subjects with elevated levels of hdl cholesterol and coronary artery disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f66898c6d66140b4838705aadba64154
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Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease

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