LDL particle subspecies are distinct in their capacity to mediate free cholesterol efflux via the SR-BI/Cla-1 receptor.
The human scavenger receptor SR-BI/Cla-1 promotes efflux of free cholesterol from cells to both high-density and low-density lipoproteins (HDL, LDL). SR-BI/Cla-1-mediated cholesterol efflux to HDL is dependent on particle size, lipid content and apolipoprotein conformation; in contrast, the capacity of LDL subspecies to accept cellular cholesterol via this receptor is indeterminate. Cholesterol efflux assays were performed with CHO cells stably transfected with Cla-1 cDNA. Expression of Cla-1 in CHO cells induced elevation in total cholesterol efflux to plasma, LDL and HDL. Such Cla-1-specific efflux was abrogated by addition of anti-Cla-1 antibody. LDL were fractionated into five subspecies either on the basis of hydrated density or size. Among LDL subfractions, small dense LDL (sdLDL) were 1.5-to 3-fold less active acceptors for Cla-1-mediated cellular cholesterol efflux. Equally, sdLDL markedly reduced Cla-1-specific cholesterol efflux to large buoyant LDL in a dose-dependent manner. Conversely, sdLDL did not influence efflux to HDL(2). These findings provide evidence that LDL particles are heterogeneous in their capacity to promote Cla-1-mediated cholesterol efflux. Relative to HDL(2), large buoyant LDL may constitute physiologically-relevant acceptors for cholesterol efflux via Cla-1.
Tréguier
Morgan
M
INSERM U551, Dyslipoproteinemia and Atherosclerosis Research Unit, Hôpital de la Pitié, 83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
Moreau
Martine
M
Sposito
Andrei
A
Chapman
M John
MJ
Huby
Thierry
T
D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002458:Cell Fractionation; D002784:Cholesterol / Q000378:metabolism* / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000502:physiology; D014162:Transfection
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D002784:Cholesterol