Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia.
OBJECTIVE
Caveolae are 50-100 nm cell surface plasma membrane invaginations observed in terminally differentiated cells. They are characterized by the presence of the protein marker caveolin-1. Caveolae and caveolin-1 are present in almost every cell type that has been implicated in the development of an atheroma. These include endothelial cells, macrophages, and smooth muscle cells. Caveolae and caveolin-1 are involved in regulating several signal transduction pathways and processes that play an important role in atherosclerosis.


RESULTS
Several recent studies using genetically engineered mice (Cav-1 (-/-) null animals) have now clearly demonstrated a role for caveolin-1 and caveolae in the development of atherosclerosis. In fact, they suggest a rather complex one, either proatherogenic or antiatherogenic, depending on the cell type examined. For example, in endothelial cells, caveolin-1 and caveolae may play a proatherogenic role by promoting the transcytosis of LDL-cholesterol particles from the blood to the sub-endothelial space. In contrast, in smooth muscle cells, the ability of caveolin-1 to negatively regulate cell proliferation (neointimal hyperplasia) may have an antiatherogenic effect.


CONCLUSIONS
Caveolin-1 and caveolae play an important role in several steps involved in the initiation of an atheroma. Development of new drugs that regulate caveolin-1 expression may be important in the prevention or treatment of atherosclerotic vascular disease.
Frank
Philippe G
PG
Department of Molecular Pharmacology and the Albert Einstein Diabetes Research and Training Center (DRTC), and Department of Urology, Albert Einstein College of Medicine, The Bronx, New York 10461, USA. pfrank@aecom.yu.edu
Lisanti
Michael P
MP
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D001692:Biological Transport; D018955:CD36 Antigens / Q000096:biosynthesis; D051242:Caveolin 1; D022461:Caveolins / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D006801:Humans; D006965:Hyperplasia; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology
C495540:CAV1 protein, human; D018955:CD36 Antigens; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D008074:Lipoproteins