Atheroprotection in the Absence of “Caves”: Is it the Fat, the Vessels, or Both?

Abstract

The protein caveolin-1 is the major coat protein for the organelle termed caveolae. Caveolae (or “small caves”) can be isolated from cells as cholesterol and sphingomyelin-enriched microdomains that are traditionally found decorating both apical and/or basolateral membranes in terminally differentiated cells. Caveolae are the primary plasmalemmal vesicle type found in vascular cells and are implicated in several basic processes, including endocytosis, potocytosis, cellular signaling, and cholesterol homeostasis.1 Work by many laboratories has placed caveolae and their less complex siblings, lipid rafts, on front and center stage in a variety of broad biology fields, including vascular biology, immunology, microbiology, and cancer biology. The article by Frank et al2 in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology sheds light on several fundamental issues regarding the role of caveolae-type vesicles in cholesterol homeostasis and atherogenesis. See page 98 Frank et al2 examine the hypothesis that caveolae-type organelles are critical for atherosclerotic lesion progression in mice. To this end, mice deficient in caveolin-1 (Cav-1−/−) and, subsequently, plasmalemmal-type caveolae3,4 were bred to mice deficient in apoliprotein E (ApoE−/−), defective in hepatic LDL cholesterol clearance. Presumptively, it was difficult to predict the net outcome on lipoprotein metabolism and lesion development in this model given the cellular data that (1) caveolin-1 is a cholesterol binding protein that can transport cholesterol from the endoplasmic reticulum to the plasma membrane5 and (2) a major receptor for HDL, scavenger receptor SR-B1, and a scavenger receptor for modified …