Caveolin-1 restoration by cholesterol enhances the inhibitory effect of simvastatin on arginine vasopressin-induced cardiac fibroblasts proliferation

Caveolin-1 (cav1) has been implicated in the regulation of cell growth, and its expression can be regulated by cellular cholesterol content. In this study, we examined the effect of manipulating cellular cholesterol content on cav1 expression and the proliferation of adult rat cardiac fibroblasts (CFs) in the presence of arginine vasopressin (AVP). We found that AVP concentration-dependently down-regulated the expression of cav1 protein. Cav1 antisense treatment enhanced the proliferatory effect of AVP. Simvastatin, a HMG-CoA reductase inhibitor, further down-regulated cav1 protein, whereas repleting cells with cholesterol increased cav1 protein and enhanced the anti-growth effect of simvastatin. Our results provide a novel finding that cholesterol restoration may confer an additional inhibitory effect over simvastatin on AVP-induced CFs proliferation through cholesterol-cav1 interaction.