Phospholipid transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis is directly correlated with HDL-cholesterol levels and is not associated with cardiovascular risk.


Journal

Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543

Informations de publication

Date de publication:
05 2021
Historique:
received: 07 07 2020
revised: 05 02 2021
accepted: 04 03 2021
pubmed: 3 4 2021
medline: 24 6 2021
entrez: 2 4 2021
Statut: ppublish

Résumé

While low concentrations of high-density lipoprotein-cholesterol (HDL-C) represent a well-established cardiovascular risk factor, extremely high HDL-C is paradoxically associated with elevated cardiovascular risk, resulting in the U-shape relationship with cardiovascular disease. Free cholesterol transfer to HDL upon lipolysis of triglyceride-rich lipoproteins (TGRL) was recently reported to underlie this relationship, linking HDL-C to triglyceride metabolism and atherosclerosis. In addition to free cholesterol, other surface components of TGRL, primarily phospholipids, are transferred to HDL during lipolysis. It remains indeterminate as to whether such transfer is linked to HDL-C and cardiovascular disease. When TGRL was labelled with fluorescent phospholipid 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), time- and dose-dependent transfer of DiI to HDL was observed upon incubations with lipoprotein lipase (LPL). The capacity of HDL to acquire DiI was decreased by -36% (p<0.001) in low HDL-C patients with acute myocardial infarction (n = 22) and by -95% (p<0.001) in low HDL-C subjects with Tangier disease (n = 7), unchanged in low HDL-C patients with Type 2 diabetes (n = 17) and in subjects with high HDL-C (n = 20), and elevated in subjects with extremely high HDL-C (+11%, p<0.05) relative to healthy normolipidemic controls. Across all the populations combined, HDL capacity to acquire DiI was directly correlated with HDL-C (r = 0.58, p<0.001). No relationship of HDL capacity to acquire DiI with both overall and cardiovascular mortality obtained from epidemiological studies for the mean HDL-C levels observed in the studied populations was obtained. These data indicate that the capacity of HDL to acquire phospholipid from TGRL upon LPL-mediated lipolysis is proportional to HDL-C and does not reflect cardiovascular risk in subjects widely differing in HDL-C levels.

Sections du résumé

BACKGROUND AND AIMS
While low concentrations of high-density lipoprotein-cholesterol (HDL-C) represent a well-established cardiovascular risk factor, extremely high HDL-C is paradoxically associated with elevated cardiovascular risk, resulting in the U-shape relationship with cardiovascular disease. Free cholesterol transfer to HDL upon lipolysis of triglyceride-rich lipoproteins (TGRL) was recently reported to underlie this relationship, linking HDL-C to triglyceride metabolism and atherosclerosis. In addition to free cholesterol, other surface components of TGRL, primarily phospholipids, are transferred to HDL during lipolysis. It remains indeterminate as to whether such transfer is linked to HDL-C and cardiovascular disease.
METHODS AND RESULTS
When TGRL was labelled with fluorescent phospholipid 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), time- and dose-dependent transfer of DiI to HDL was observed upon incubations with lipoprotein lipase (LPL). The capacity of HDL to acquire DiI was decreased by -36% (p<0.001) in low HDL-C patients with acute myocardial infarction (n = 22) and by -95% (p<0.001) in low HDL-C subjects with Tangier disease (n = 7), unchanged in low HDL-C patients with Type 2 diabetes (n = 17) and in subjects with high HDL-C (n = 20), and elevated in subjects with extremely high HDL-C (+11%, p<0.05) relative to healthy normolipidemic controls. Across all the populations combined, HDL capacity to acquire DiI was directly correlated with HDL-C (r = 0.58, p<0.001). No relationship of HDL capacity to acquire DiI with both overall and cardiovascular mortality obtained from epidemiological studies for the mean HDL-C levels observed in the studied populations was obtained.
CONCLUSIONS
These data indicate that the capacity of HDL to acquire phospholipid from TGRL upon LPL-mediated lipolysis is proportional to HDL-C and does not reflect cardiovascular risk in subjects widely differing in HDL-C levels.

Identifiants

pubmed: 33798922
pii: S0021-9150(21)00110-6
doi: 10.1016/j.atherosclerosis.2021.03.002
pii:
doi:

Substances chimiques

Lipoproteins, HDL 0
Phospholipids 0
Triglycerides 0
Cholesterol 97C5T2UQ7J
Lipoprotein Lipase EC 3.1.1.34

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1-8

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Feng Ma (F)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France. Electronic address: feng.ma@siat.ac.cn.

Maryam Darabi (M)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Marie Lhomme (M)

Institute of Cardiometabolism and Nutrition (ICAN), Paris, F-75013, France.

Emilie Tubeuf (E)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Aurélie Canicio (A)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Jean Brerault (J)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Narcisse Medadje (N)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Fabiana Rached (F)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France; Heart Institute-InCor, University of Sao Paulo, Sao Paulo, Brazil.

Sandrine Lebreton (S)

Sorbonne University, Paris, France.

Eric Frisdal (E)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Fernando Brites (F)

Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, INFIBIOC, University of Buenos Aires, CONICET. Buenos Aires, Argentina.

Carlos Serrano (C)

Heart Institute-InCor, University of Sao Paulo, Sao Paulo, Brazil.

Raul Santos (R)

Heart Institute-InCor, University of Sao Paulo, Sao Paulo, Brazil.

Emmanuel Gautier (E)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Thierry Huby (T)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Petra El Khoury (P)

Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Pôle Technologie-Santé, Saint Joseph University, Beirut, Lebanon; INSERM LVTS U1148, Hôpital Bichat-Claude Bernard, Paris, France.

Alain Carrié (A)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Marianne Abifadel (M)

Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Pôle Technologie-Santé, Saint Joseph University, Beirut, Lebanon; INSERM LVTS U1148, Hôpital Bichat-Claude Bernard, Paris, France.

Eric Bruckert (E)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France; Institute of Cardiometabolism and Nutrition (ICAN), Paris, F-75013, France; AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris, F-75013, France.

Maryse Guerin (M)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Philippe Couvert (P)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Philippe Giral (P)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France; Institute of Cardiometabolism and Nutrition (ICAN), Paris, F-75013, France; AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris, F-75013, France.

Philippe Lesnik (P)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Wilfried Le Goff (W)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Isabelle Guillas (I)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

Anatol Kontush (A)

National Institute for Health and Medical Research (INSERM) UMR_S 1166, Faculty of Medicine Pitie-Salpetriere, 91 Bld de L'Hopital, 75013, Paris, France; Sorbonne University, Paris, France.

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