Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospholipids: relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and antiapoptotic functionalities
| Autor: | Marie Lhomme, Laurent Camont, Michel Lagarde, Anne Nègre-Salvayre, Wilfried Le Goff, Fabiana Rached, M. John Chapman, Anatol Kontush, Catherine Calzada, Robert Salvayre |
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| Přispěvatelé: | Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Dyslipidémies, inflammation et athérosclérose dans les maladies métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM), Heart Institute-InCor, Faculdade de Medicina da Universidade de São Paulo-Medical School Hospital, Service de Biochimie, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Simon, Marie Francoise, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
MESH: Inflammation MESH: Oxidation-Reduction MESH: Lipoproteins LDL MESH: Lipoproteins HDL3 Apoptosis 030204 cardiovascular system & hematology MESH: Atherosclerosis chemistry.chemical_compound 0302 clinical medicine MESH: Cholesterol Tandem Mass Spectrometry MESH: Endothelial Cells Phospholipids MESH: Blood Platelets MESH: Aged 0303 health sciences MESH: Middle Aged MESH: Oxidative Stress Lipoproteins HDL3 Phosphatidylserine Phosphatidic acid Middle Aged Lipoproteins LDL Lysophosphatidylcholine Cholesterol Biochemistry lipids (amino acids peptides and proteins) Inflammation Mediators Cardiology and Cardiovascular Medicine Sphingomyelin Oxidation-Reduction Adult Blood Platelets Ceramide MESH: Cell Line Tumor MESH: Inflammation Mediators Phospholipid Biology Ceramides MESH: Sphingolipids 03 medical and health sciences Cell Line Tumor Humans MESH: Particle Size MESH: Thrombosis Particle Size 030304 developmental biology Aged Phosphatidylethanolamine Inflammation MESH: Phospholipids Sphingolipids MESH: Humans Macrophages MESH: Apoptosis Endothelial Cells MESH: Macrophages MESH: Tandem Mass Spectrometry Thrombosis MESH: Adult Atherosclerosis Sphingolipid MESH: Ceramides MESH: Male Oxidative Stress chemistry MESH: Chromatography Liquid Chromatography Liquid |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2013, 33 (12), pp.2715-23. ⟨10.1161/ATVBAHA.113.301468⟩ Arteriosclerosis, Thrombosis, and Vascular Biology, 2013, 33 (12), pp.2715-23. ⟨10.1161/ATVBAHA.113.301468⟩ |
| ISSN: | 1079-5642 1524-4636 |
| DOI: | 10.1161/ATVBAHA.113.301468⟩ |
| Popis: | Objective— High-density lipoprotein (HDL) displays multiple atheroprotective activities and is highly heterogeneous in structure, composition, and function; the molecular determinants of atheroprotective functions of HDL are incompletely understood. Because phospholipids represent a major bioactive lipid component of HDL, we characterized the phosphosphingolipidome of major normolipidemic HDL subpopulations and related it to HDL functionality. Approach and Results— Using an original liquid chromatography–mass spectrometry/mass spectrometry methodology for phospholipid and sphingolipid profiling, 162 individual molecular lipid species were quantified across the 9 lipid subclasses, in the order of decreasing abundance, phosphatidylcholine>sphingomyelin>lysophosphatidylcholine>phosphatidylethanolamine>phosphatidylinositol>ceramide>phosphatidylserine>phosphatidylglycerol>phosphatidic acid. When data were expressed relative to total lipid, the contents of lysophosphatidylcholine and of negatively charged phosphatidylserine and phosphatidic acid increased progressively with increase in hydrated density of HDL, whereas the proportions of sphingomyelin and ceramide decreased. Key biological activities of HDL subpopulations, notably cholesterol efflux capacity from human THP-1 macrophages, antioxidative activity toward low-density lipoprotein oxidation, antithrombotic activity in human platelets, cell-free anti-inflammatory activity, and antiapoptotic activity in endothelial cells, were predominantly associated with small, dense, protein-rich HDL3. The biological activities of HDL particles were strongly intercorrelated, exhibiting significant correlations with multiple components of the HDL phosphosphingolipidome. Specifically, the content of phosphatidylserine revealed positive correlations with all metrics of HDL functionality, reflecting enrichment of phosphatidylserine in small, dense HDL3. Conclusions— Our structure–function analysis thereby reveals that the HDL lipidome may strongly affect atheroprotective functionality. |
| Databáze: | OpenAIRE |
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