Assistant Professor

Cancer Biology

Thomas Jefferson University (Philadelphia, PA)

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 important roles in atherosclerosis.
Heart disease is a leading cause of death in the United States and the Western World. A deep understanding of the events leading to heart disease is necessary in order to prevent and properly treat this deadly illness. o­ne important clue is the role of fat and especially cholesterol in this process. High blood cholesterol levels are a major risk factor for heart disease, and the underlying disease process --more broadly termed atherosclerosis.During this process, the “bad” cholesterol is deposited in the blood vessels, leading to the formation of a blockage. Ultimately, we must understand the mechanisms by which occlusions form to prevent their development. Recent studies using genetically-engineered mice (Cav-1(-/-) knock-out 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 pro-atherogenic or anti-atherogenic, depending o­n the cell type examined. For example, in endothelial cells, caveolin-1 and caveolae may play a pro-atherogenic role by promoting the transcytosis of low-density lipoprotein (LDL) particles from the blood to the sub-endothelial space. In contrast, in smooth muscle cells, caveolin-1’s ability to negatively regulate cell proliferation (neointimal hyperplasia) may be anti-atherogenic. In addition, macrophage caveolin-1 may have a protective effect by preventing cholesteryl ester accumulation in macrophages.