Influence of caveolin-1 on cellular cholesterol efflux mediated by high-density lipoproteins

Caveolin-1 is a principal structural component of caveolae membranes. These membrane microdomains participate in the regulation of signaling, transcyt osis, and cholesterol homeostasis at the plasma membrane. In the present st udy, we determined the effect of caveolin-1 expression on cellular choleste rol efflux mediated by high-density lipoprotein (HDL). We evaluated this ef fect in parental NIH/3T3 cells as well as in two transformed NIH/3T3 cell l ines in which caveolin-1 protein levels are dramatically downregulated. Com pared with parental NIH/3T3 cells, these two transformed cell lines effluxe d cholesterol more rapidly to HDL. In addition, NIH/3T3 cells harboring cav eolin-1 antisense also effluxed cholesterol more rapidly to HDL. However, t his effect was not due to changes in total cellular cholesterol content. We further showed that chronic HDL exposure reduced caveolin-1 protein expres sion in NIH/3T3 cells. HDL exposure also inhibited caveolin-1 promoter acti vity, suggesting a direct negative effect of HDL on caveolin-1 gene transcr iption. Moreover, we showed that HDL-induced downregulation of caveolin-1 p revents the uptake of oxidized low-density lipoprotein in human endothelial cells. These data suggest a novel proatherogenic role for caveolin-1, i.e. , regarding the uptake and/or transcytosis of modified lipoproteins.