SR-BI et métabolisme du cholestérol

Abstract

Dans la classe des recepteurs " eboueurs " (scavenger), le SR-BI (scavenger receptor class B type 1) murin, dont l' homologue humain est CLA1 (CD36 and LIMPII analogous-1), possede la fonction inattendue de lier les HDL, facilitant l' entree selective du cholesterol esterifie des HDL dans la cellule. On sait depuis longtemps que ce mode d' acquisition du cholesterol concerne les organes utilisateurs de cholesterol comme le foie et les tissus steroidogenes. Cependant, l' implication de SR-BI dans ce processus permet de mieux comprendre son mecanisme. L' utilisation de souris exprimant SR-BI a des degres divers a revele le role majeur de cette proteine dans le controle de la concentration plasmatique des HDL. Cependant, la surexpression hepatique de SR-BI produit non seulement une chute des HDL plasmatiques, mais reduit egalement la concentration des VLDL et des LDL, lipoproteines atherogenes. SR-BI interviendrait aussi dans le flux sortant de cholesterol cellulaire, l' elimination du cholesterol biliaire et l' absorption intestinale des lipides. La decouverte recente de ce role multiple de la proteine SR-BI dans la dynamique du cholesterol ouvre de nouvelles perspectives dans le traitement des maladies du metabolisme du cholesterol.

As a member of the scavenger receptor family, the murine SR-BI (human homolog: CLA1) acts unexpectedly as a HDL-binding protein involved in the selective uptake of HDL cholesteryl esters (HDL-CE). The delivery of HDL-CE to hepatic and steroidogenic tissues has been established for decades, but its precise mechanism was unclear. As SR-BI has been shown to be involved in this process, the mechanism can now be better understood. The use of transgenic mice, differing in their degree of SR-BI expression, has revealed that this HDL-receptor plays a major role in regulating the plasma HDL levels. These studies indicated that the specific overexpression of SR-BI in liver produces not only a dramatic fall of circulating HDL, but also a significant reduction in atherogenic lipoproteins, VLDL and LDL. These effects were associated with a reduction of atherosclerotic lesions in animals fed an atherogenic diet. In addition, SR-BI has also been implicated in cellular cholesterol efflux, biliary secretion of cholesterol from the hepatocytes and intestinal absorption of lipids. These exciting discoveries raise the possibility that further investigations may offer novel approaches to the prevention and treatment of cholesterol related diseases such as atherosclerosis and cholelithiasis.