Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]

To evaluate functional and compositional properties of HDL in subjects from a kindred of genetic apoA-I deficiency, two homozygotes and six heterozygotes, with a nonsense mutation at APOA1 codon -2, Q[-2]X, were recruited together with age- and sex-matched healthy controls (n = 11). Homozygotes disp...

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Main Authors:	Fabiana Rached, Raul D. Santos, Laurent Camont, Marcio H. Miname, Marie Lhomme, Carolane Dauteuille, Sora Lecocq, Carlos V. Serrano, Jr., M. John Chapman, Anatol Kontush
Format:	Article
Language:	English
Published:	Elsevier 2014-12-01
Series:	Journal of Lipid Research
Subjects:	high density lipoprotein apolipoprotein A-I familial deficiency genetics HDL functionality cellular cholesterol efflux
Online Access:	http://www.sciencedirect.com/science/article/pii/S0022227520366918

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spelling	doaj-18217a71a2294fb0940deceb284fb8da2021-04-28T06:01:14ZengElsevierJournal of Lipid Research0022-22752014-12-01551225092520Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]Fabiana Rached0Raul D. Santos1Laurent Camont2Marcio H. Miname3Marie Lhomme4Carolane Dauteuille5Sora Lecocq6Carlos V. Serrano, Jr.7M. John Chapman8Anatol Kontush9National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6, Pitié – Salpétrière University Hospital, ICAN, Paris, France; Heart Institute-InCor, University of Sao Paulo, Sao Paulo, BrazilHeart Institute-InCor, University of Sao Paulo, Sao Paulo, BrazilNational Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6, Pitié – Salpétrière University Hospital, ICAN, Paris, FranceHeart Institute-InCor, University of Sao Paulo, Sao Paulo, BrazilNational Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6, Pitié – Salpétrière University Hospital, ICAN, Paris, FranceNational Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6, Pitié – Salpétrière University Hospital, ICAN, Paris, FranceNational Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6, Pitié – Salpétrière University Hospital, ICAN, Paris, FranceHeart Institute-InCor, University of Sao Paulo, Sao Paulo, BrazilNational Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6, Pitié – Salpétrière University Hospital, ICAN, Paris, FranceTo whom correspondence should be addressed; National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6, Pitié – Salpétrière University Hospital, ICAN, Paris, France; To whom correspondence should be addressedTo evaluate functional and compositional properties of HDL in subjects from a kindred of genetic apoA-I deficiency, two homozygotes and six heterozygotes, with a nonsense mutation at APOA1 codon -2, Q[-2]X, were recruited together with age- and sex-matched healthy controls (n = 11). Homozygotes displayed undetectable plasma levels of apoA-I and reduced levels of HDL-cholesterol (HDL-C) and apoC-III (5.4% and 42.6% of controls, respectively). Heterozygotes displayed low HDL-C (21 ± 9 mg/dl), low apoA-I (79 ± 24 mg/dl), normal LDL-cholesterol (132 ± 25 mg/dl), and elevated TG (130 ± 45 mg/dl) levels. Cholesterol efflux capacity of ultracentrifugally isolated HDL subpopulations was reduced (up to −25%, P < 0.01, on a glycerophospholipid [GP] basis) in heterozygotes versus controls. Small, dense HDL3 and total HDL from heterozygotes exhibited diminished antioxidative activity (up to −48%, P < 0.001 on a total mass basis) versus controls. HDL subpopulations from both homozygotes and heterozygotes displayed altered chemical composition, with depletion in apoA-I, GP, and cholesteryl ester; enrichment in apoA-II, free cholesterol, and TG; and altered phosphosphingolipidome. The defective atheroprotective activities of HDL were correlated with altered lipid and apo composition. These data reveal that atheroprotective activities of HDL particles are impaired in homozygous and heterozygous apoA-I deficiency and are intimately related to marked alterations in protein and lipid composition.http://www.sciencedirect.com/science/article/pii/S0022227520366918high density lipoproteinapolipoprotein A-Ifamilial deficiencygeneticsHDL functionalitycellular cholesterol efflux
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Fabiana Rached Raul D. Santos Laurent Camont Marcio H. Miname Marie Lhomme Carolane Dauteuille Sora Lecocq Carlos V. Serrano, Jr. M. John Chapman Anatol Kontush
spellingShingle	Fabiana Rached Raul D. Santos Laurent Camont Marcio H. Miname Marie Lhomme Carolane Dauteuille Sora Lecocq Carlos V. Serrano, Jr. M. John Chapman Anatol Kontush Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S] Journal of Lipid Research high density lipoprotein apolipoprotein A-I familial deficiency genetics HDL functionality cellular cholesterol efflux
author_facet	Fabiana Rached Raul D. Santos Laurent Camont Marcio H. Miname Marie Lhomme Carolane Dauteuille Sora Lecocq Carlos V. Serrano, Jr. M. John Chapman Anatol Kontush
author_sort	Fabiana Rached
title	Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]
title_short	Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]
title_full	Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]
title_fullStr	Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]
title_full_unstemmed	Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]
title_sort	defective functionality of hdl particles in familial apoa-i deficiency: relevance of alterations in hdl lipidome and proteome[s]
publisher	Elsevier
series	Journal of Lipid Research
issn	0022-2275
publishDate	2014-12-01
description	To evaluate functional and compositional properties of HDL in subjects from a kindred of genetic apoA-I deficiency, two homozygotes and six heterozygotes, with a nonsense mutation at APOA1 codon -2, Q[-2]X, were recruited together with age- and sex-matched healthy controls (n = 11). Homozygotes displayed undetectable plasma levels of apoA-I and reduced levels of HDL-cholesterol (HDL-C) and apoC-III (5.4% and 42.6% of controls, respectively). Heterozygotes displayed low HDL-C (21 ± 9 mg/dl), low apoA-I (79 ± 24 mg/dl), normal LDL-cholesterol (132 ± 25 mg/dl), and elevated TG (130 ± 45 mg/dl) levels. Cholesterol efflux capacity of ultracentrifugally isolated HDL subpopulations was reduced (up to −25%, P < 0.01, on a glycerophospholipid [GP] basis) in heterozygotes versus controls. Small, dense HDL3 and total HDL from heterozygotes exhibited diminished antioxidative activity (up to −48%, P < 0.001 on a total mass basis) versus controls. HDL subpopulations from both homozygotes and heterozygotes displayed altered chemical composition, with depletion in apoA-I, GP, and cholesteryl ester; enrichment in apoA-II, free cholesterol, and TG; and altered phosphosphingolipidome. The defective atheroprotective activities of HDL were correlated with altered lipid and apo composition. These data reveal that atheroprotective activities of HDL particles are impaired in homozygous and heterozygous apoA-I deficiency and are intimately related to marked alterations in protein and lipid composition.
topic	high density lipoprotein apolipoprotein A-I familial deficiency genetics HDL functionality cellular cholesterol efflux
url	http://www.sciencedirect.com/science/article/pii/S0022227520366918
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Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome[S]

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