Philippe G. Frank, Ph.D.


Assistant Professor
Cancer Biology

Telephone
215-503-9292

Office Address
933 BLSB
233 S. 10th St.

Email Address
Philippe.Frank@jefferson.edu

 

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.



Keywords: Atherosclerosis, Lipoprotein, Cholesterol, Caveolae
 

PubMed Link For Frank PG


Selected Publications

Frank PG, Hassan GS, Rodriguez-Feo JA, Lisanti MP. Caveolae and caveolin-1: novel potential targets for the treatment of cardiovascular disease. Curr Pharm Des. 13(17):1761-9, 2007. ( Abstract )

Frank PG, Lisanti MP. Caveolin-1 and liver regeneration: role in proliferation and lipogenesis. Cell Cycle. 6(2):115-6, 2007. ( Abstract )

Frank PG, Lisanti MP. Zebrafish as a novel model system to study the function of caveolae and caveolin-1 in organismal biology. Am J Pathol. 169(6):1910-2, 2006. ( Abstract )

Frank PG, Lisanti MP. Role of caveolin-1 in the regulation of the vascular shear stress response. J Clin Invest. 116(5):1222-5, 2006. ( Abstract )

Frank PG, Cheung MW, Pavlides S, Llaverias G, Park DS, Lisanti MP. Caveolin-1 and regulation of cellular cholesterol homeostasis. Am J Physiol Heart Circ Physiol. 291(2):H677-86, 2006. ( Abstract )

Frank PG, Lisanti MP. Defining lipid raft structure and function with proximity imaging. Am J Physiol Heart Circ Physiol. 290(6):H2165-6, 2006. ( Abstract )

Hassan GS, Williams TM, Frank PG, Lisanti MP. Caveolin-1-deficient aortic smooth muscle cells show cell autonomous abnormalities in proliferation, migration, and endothelin-based signal transduction. Am J Physiol Heart Circ Physiol. 290(6):H2393-401, 2006. ( Abstract )

Li J, Scherl A, Medina F, Frank PG, Kitsis RN, Tanowitz HB, Sotgia F, Lisanti MP. Impaired phagocytosis in caveolin-1 deficient macrophages. Cell Cycle. 4(11):1599-607, 2005. ( Abstract )

Williams TM, Hassan GS, Li J, Cohen AW, Medina F, Frank PG, Pestell RG, Di Vizio D, Loda M, Lisanti MP. Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: genetic ablation of Cav-1 delays advanced prostate tumor development in tramp mice. J Biol Chem. 280(26):25134-45, 2005. ( Abstract )

Roy S, Hyogo H, Yadav SK, Wu MK, Jelicks LA, Locker JD, Frank PG, Lisanti MP, Silver DL, Cohen DE. A biphasic response of hepatobiliary cholesterol metabolism to dietary fat at the onset of obesity in the mouse. Hepatology. 41(4):887-95, 2005. ( Abstract )

Frank PG, Lisanti MP. Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia. Curr Opin Lipidol. 15(5):523-9, 2004. ( Abstract )

Hassan GS, Jasmin JF, Schubert W, Frank PG, Lisanti MP. Caveolin-1 deficiency stimulates neointima formation during vascular injury. Biochemistry. 43(26):8312-21, 2004. ( Abstract )
 

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