title: Pravastatin reverses the membrane cholesterol reorganization induced by myocardial infarction within lipid rafts in CD14(+)/CD16(-) circulating monocytes.
abstract: Large numbers of monocytes are recruited in the infarcted myocardium. Their cell membranes contain cholesterol-rich microdomains called lipids rafts, which participate in numerous signaling cascades. In addition to its cholesterol-lowering effect, pravastatin has several pleiotropic effects and is widely used as secondary prevention treatment after myocardial infarction (MI). The aim of this study was to investigate the effects of pravastatin on the organization of cholesterol within monocyte membrane rafts from patients who had suffered myocardial infarction. Monocytes from healthy donors and acute MI patients were cultured with or without 4μM pravastatin. Lipid rafts were extracted by Lubrol WX, caveolae and flat rafts were separated using a modified sucrose gradient. Cholesterol level and caveolin-1 expression in lipid rafts were determined. In healthy donors, cholesterol was concentrated in flat rafts (63±3 vs 13±1%, p<0.001). While monocytes from MI patients presented similar cholesterol distribution in both caveolae and flat rafts. Cholesterol distribution was higher in flat rafts in healthy donors, compared to MI patients (63±3 vs 41±2%, p<0.001), with less distribution in caveolae (13±1 vs 34±2%, p<0.001). Pravastatin reversed the cholesterol distribution in MI patients cells between flat rafts (41±2 vs 66±3%, p<0.001) and caveolae (34±2 vs 18±1%, p<0.001). In conclusion, MI redistributes cholesterol from flat rafts to caveolae indicating monocyte membrane reorganization. In vitro pravastatin treatment restored basal conditions in MI monocytes, suggesting another effect of statins.
authors.affiliation: IFR100 SANTE-STIC-INSERM, Université de Bourgogne, Dijon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Salvary
authors.forename: Ségolène
authors.initials: S
authors.lastname: Gambert-Nicot
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Brindisi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meneveau
authors.forename: François
authors.initials: F
authors.lastname: Schiele
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Séronde
authors.forename: Luc
authors.initials: L
authors.lastname: Lorgis
authors.forename: Marianne
authors.initials: M
authors.lastname: Zeller
authors.forename: Yves
authors.initials: Y
authors.lastname: Cottin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kantelip
authors.forename: Philippe
authors.initials: P
authors.lastname: Gambert
authors.forename: Siamak
authors.initials: S
authors.lastname: Davani
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D021941:Caveolae / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000096:biosynthesis; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D017035:Pravastatin / Q000494:pharmacology*; D017452:Receptors, IgG
chemical_list: D000924:Anticholesteremic Agents; C495540:CAV1 protein, human; D051242:Caveolin 1; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D002784:Cholesterol; D017035:Pravastatin