Caveolin-1: Dual Role for Proliferation of Vascular Smooth Muscle Cells

Although caveolae function in vesicular and cholesterol trafficking, the recent identification of various signaling molecules in caveolae and their functional interaction with caveolin suggest that they may participate in transmembrane signaling. Interestingly, many of the signaling molecules that interact with caveolin-1 (cav-1) mediate mitogenic signals to the nucleus, implying that cav-1 may play a modulating role in the pathophysiology of vascular proliferative diseases such as atherosclerosis and restenosis after angioplasty. Although much attention has been given to the predominantly antiproliferative role of cav-1 in growth-factor-induced signal transduction, we were recently able to demonstrate that cav-1 acts in mechanotransduction too. During cyclic strain, however, cav-1 is critically involved in proproliferative signaling. We propose that, at least in the vasculature which is constantly exposed to alternating mechanical force and different growth factors, cav-1 holds a dual role toward modulation of proliferation, depending on the stimulus the cells are exposed to. In vivo, the net effect of growth factors and mechanically triggered stimuli determines the amount of local cell proliferation and, therefore, the onset and progression of vascular proliferative disease.