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Victor Rizzo, PhD
Associate Professor, Anatomy and Cell Biology Telephone: 215-707-9863; 215-707-6046 (lab) Fax: 215-707-5737 Office; Medical Research Room 826A Email: victor.rizzo@temple.edu
Department of Anatomy and Cell BiologyCardiovascular Research Center
Endothelial cells are uniquely positioned between the blood and tissue compartments and directly encounter the fluid forces generated by blood flowing through the vasculature. These hemodynamic forces appear to play a central role in the acute and chronic regulation of the structural and functional phenotype of the endothelium. Because inadequate or inappropriate adjustment to alterations in flow is associated with vascular pathophysiology such as hypertension, atherosclerosis and stroke, deciphering the molecular signaling elements that detect and transmit hemodynamic changes within the endothelium holds potential clinical relevance. Although much attention has focused on understanding the molecular signaling mechanisms that transmit hemodynamic forces into the cell, the flow-sensing mechanism or mechanoreceptor purported to exist in the endothelial cell remains to be identified. The recent discovery that many receptors and signaling molecules preferentially localize to cholesterol and sphingolipids rich regions of the plasma membrane, termed lipid rafts and caveolae, has lead to the hypothesis that these plasma membrane microdomains also serve as signaling compartments. Since many of the signaling molecules shown to reside in lipid rafts and caveolae have been implicated in transduction of fluid mechanical forces, we hypothesize that plasma membrane caveolae function as mechanotransduction centers. Using a unique methodology which allows for the purification and subfractionation of the luminal endothelial cell plasma membrane, we showed evidence that cell surface mechano-chemical signaling can occur within caveolae microdomains. Through biochemical, immunohistological, molecular genetic and unique in vivo and in vitro methodological approaches, our ongoing studies are designed to further investigate the physiological role of caveolae in cardiovascular health and disease.
DeFouw DO, Rizzo VJ, Steinfeld R and Feinberg RN: Mapping of the microcirculation in the chick chorioallantoic membrane during normal angiogenesis. Microvasc. Res. 38:136-147, 1989
Rizzo V, Steinfeld R, Kyriakides C and DeFouw DO: The microvascular unit of the 6-day chick choriallantoic membrane: A fluorescent confocal microscopic and ultrastructural morphometric analysis of endothelial permselectivity. Microvasc. Res. 46:320-332, 1993.
Rizzo V and DeFouw DO: Macromolecular selectivity of chick chorioallantoic membrane microvessels during normal angiogenesis and endothelial differentiation. Tissue and Cell 25:847-856, 1993.
Rizzo V, Kim D, Duran WN and DeFouw DO: Ontogeny of microvascular permeability to macromolecules in the chick chorioallantoic membrane during normal angiogenesis. Microvasc. Res. 49:49-63, 1995.
Rizzo V, Kim D, Duran WN and DeFouw DO: Differentiation of the microvascular endothelium during normal angiogenesis and respiratory onset in the chick chorioallantoic membrane. Tissue and Cell 27:159-166, 1995.
Rizzo V and DeFouw DO: Capillary sprouts restrict macromolecular extravasation during normal angiogenesis in the chick chorioallantoic membrane. Microvasc. Res. 52:47-51, 1996.
Rizzo V, Shumko JZ and DeFouw DO: Degranulation of mast cells in the chick chorioallantoic membrane does not increase endothelial permselectivity during normal angiogenesis. Microcirculation 3:387-393, 1996.
Rizzo V and DeFouw DO: Mast cell activation accelerates the normal rate of angiogenesis in the chorioallantoic membrane. Microvasc. Res. 52:245-257, 1996.
Rizzo V and DeFouw DO: Microvascular permselectivity in the chick chorioallantoic membrane during endothelial cell senescence. Int.J. Microcirc. 17:75-79, 1997.
Rizzo V, Cruz A and DeFouw DO: Microvessels of the chorioallantoic membrane uniformly restrict albumin extravasation during angiogenesis and endothelial differentiation. Tissue and Cell 29:277-281, 1997.
Rizzo V, Sung A, Oh P, and Schnitzer JE. Rapid mechanotransduction in situ at the luminal cell surface of the microvascular endothelium and its caveolae. J. Biol. Chem. 273:26323-26329, 1998.
Rizzo V, McIntosh DP, Oh P, and Schnitzer JE. Flow activates eNOS in caveolae at the luminal cell surface of endothelium in situ with rapid caveolin dissociation and calmodulin association. J. Biol. Chem. 273:34724-34729. 1998.
Rizzo V and Schnitzer JE: In: Vascular endothelium: Mechanisms of Cell signaling. Ed. Catravas, J.D., Callow, A.D. and Ryan, U.S.; Role of Caveolae in mechanotransduction, IOS Press, NATO Science Series A, vol 308, pp.97-116, 1999.
Dr. Rizzo Lab is located MRB 826A 215-707-6046 Graduate Students: Michelle D Heayn michelle.heayn@temple.edu Harinder Singh harinder.singh@temple.edu
Baohua Yang, DVM, PhD Associate Scientist Lab Manager T: 215-707-6046 F: 215-707-5737 Email address: baohua.yang@temple.edu
Theresa Slaughter Lab Technician T: 215-707-1741 Email address: theresa.slaughter@temple.edu
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