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Victor Rizzo, PhD, FAHA
Professor, Anatomy and Cell Biology
Professor, Cardiovascular Research Center
Professor, Sol Sherry Thrombosis Research Center
Telephone: 215-707-9863; 215-707-6046 (lab)
Office: MERB 1080
Department of Anatomy and Cell Biology
Cardiovascular Research Center
Sol Sherry Thrombosis Research Center
BS, Biology - Farleigh Dickinson University
PhD, Cell Biology, Angiogenesis - New Jersey Medical School
Postdoctoral Fellow, Caveolae - Harvard Medical School
- University of Pennsylvania
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Overview: The long-range goal of the Rizzo lab is to discover the molecular signaling mechanisms that contribute to endothelial dysfunction and associated cardiovascular diseases such as atherosclerosis and aneurysm formation. Past studies demonstrate the importance of caveolae organelles in regulating endothelial cell function. Primarily described as transport vesicles involved in the processes of endocytosis and transcytosis, more recent studies have garnered great interest in caveolae because of their role in signaling. Caveolin, which is a principle protein component of caveolar membranes, directly interacts with a variety of signaling molecules. These signaling molecules become activated once receptor binding occurs in caveolae. The localization of receptors and signaling molecules within these microdomains likely provides the proximity necessary for rapid, efficient and specific propagation of signals to downstream targets. Our research program offers the opportunity to evaluate the physiologic and pathophysiologic roles of caveolae and caveolin in signaling and transport using modern techniques in microscopy, biochemistry, cell biology molecular genetic and unique in vivo and in vitro methodological approaches. The following are brief descriptions of the laboratories current research focus.
- Mechanotransduction: Atherosclerotic plaques are most often found where blood vessels bifurcate. The flow of blood within these regions is chaotic and turbulent, which alters the normal function of the endothelium. In addition, these flow patterns are associated with the development of abdominal aortic aneurysms. Our primary interest in this area is to uncover the mechanism by which hemodynamics contribute to endothelial dysfunction and describe meaningful elements of the mechanotransduction process. Thus far, our work has identified caveolae, as sites where fluid mechanical forces generated by flowing blood are detected and converted into a biochemical signals within the endothelial cells. Our ongoing project is designed to test the concept that caveolae serve as membrane sites for integration of input and output mechanotransducing signals. The rationale that underlies this research is that, once a clear understanding of the mechanotransduction pathways are achieved, relevant components may be targeted to attenuate disease initiation and/or progression in hemodynamic sensitive areas of the vasculature.
- Oxidative stress: There is mounting evidence that oxidative stress is a significant contributor to endothelial dysfunction and associated vascular pathologies. Surprisingly, results from clinical trials show little benefit of broad antioxidant therapy on cardiovascular events. In order to overcome this limitation, a deeper understanding of the mechanisms that regulate oxidant production and the role of oxidants in endothelial dysfunction is needed. Based on our past findings, we propose a project objective which will determine how caveolae/caveolin-1 regulate a major oxidant-producing enzyme system in the endothelium, NADPH oxidases (Nox). Our central hypothesis is that subcellular positioning of Nox in caveolae provides a mechanism for regulation of oxidant production and compartmentalization of redox signaling that contribute to endothelial dysfunction.
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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.
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Dr. Rizzo Lab is located MERB 1080 215-707-6046
Kevin Crawford firstname.lastname@example.org
Michelle D Heayn email@example.com
Harinder Singh firstname.lastname@example.org
Allison Andrews, PhD email@example.com
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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)
23567617. Liu Y, Dillon AR, Tillson M, Makarewich C, Nguyen V, Dell'italia L, Sabri AK, Rizzo V, Tsai EJ, Volume overload induces differential spatiotemporal regulation of myocardial soluble guanylyl cyclase in eccentric hypertrophy and heart failure. J Mol Cell Cardiol 60C:(72-83)2013 Apr 6
22544282. Macaluso M, Caracciolo V, Rizzo V, Sun A, Montanari M, Russo G, Bellipanni G, Khalili K, Giordano A, Integrating role of T antigen, Rb2/p130, CTCF and BORIS in mediating non-canonical endoplasmic reticulum-dependent death pathways triggered by chronic ER stress in mouse medulloblastoma. Cell Cycle 11:9(1841-50)2012 May 1
22302787. Makarewich CA, Correll RN, Gao H, Zhang H, Yang B, Berretta RM, Rizzo V, Molkentin JD, Houser SR, A caveolae-targeted L-type Ca▓+ channel antagonist inhibits hypertrophic signaling without reducing cardiac contractility. Circ Res 110:5(669-74)2012 Mar 2
22158875. Gabunia K, Ellison SP, Singh H, Datta P, Kelemen SE, Rizzo V, Autieri MV, Interleukin-19 (IL-19) induces heme oxygenase-1 (HO-1) expression and decreases reactive oxygen species in human vascular smooth muscle cells. J Biol Chem 287:4(2477-84)2012 Jan 20
21796257. Feairheller DL, Park JY, Rizzo V, Kim B, Brown MD, Racial differences in the responses to shear stress in human umbilical vein endothelial cells. Vasc Health Risk Manag 7:(425-31)2011
21172357. Takaguri A, Shirai H, Kimura K, Hinoki A, Eguchi K, Carlile-Klusacek M, Yang B, Rizzo V, Eguchi S, Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth factor receptor transactivation by angiotensin II. J Mol Cell Cardiol 50:3(545-51)2011 Mar
21051664. Yang B, Radel C, Hughes D, Kelemen S, Rizzo V, p190 RhoGTPase-activating protein links the ▀1 integrin/caveolin-1 mechanosignaling complex to RhoA and actin remodeling. Arterioscler Thromb Vasc Biol 31:2(376-83)2011 Feb
19452279. Rosano JM, Tousi N, Scott RC, Krynska B, Rizzo V, Prabhakarpandian B, Pant K, Sundaram S, Kiani MF, A physiologically realistic in vitro model of microvascular networks. Biomed Microdevices 11:5(1051-7)2009 Oct
17928535. Rizzo V, Lights, camera, actin! The cytoskeleton takes center stage in mechanotransduction. Focus on "Mapping the dynamics of shear stress-induced structural changes in endothelial cells.". Am J Physiol Cell Physiol 293:6(C1771-2)2007 Dec
17585065. Wu Y, Rizzo V, Liu Y, Sainz IM, Schmuckler NG, Colman RW, Kininostatin associates with membrane rafts and inhibits alpha(v)beta3 integrin activation in human umbilical vein endothelial cells. Arterioscler Thromb Vasc Biol 27:9(1968-75)2007 Sep
17498653. Radel C, Carlile-Klusacek M, Rizzo V, Participation of caveolae in beta1 integrin-mediated mechanotransduction. Biochem Biophys Res Commun 358:2(626-31)2007 Jun 29
17369462. Carlile-Klusacek M, Rizzo V, Endothelial cytoskeletal reorganization in response to PAR1 stimulation is mediated by membrane rafts but not caveolae. Am J Physiol Heart Circ Physiol 293:1(H366-75)2007 Jul
17028163. Yang B, Rizzo V, TNF-alpha potentiates protein-tyrosine nitration through activation of NADPH oxidase and eNOS localized in membrane rafts and caveolae of bovine aortic endothelial cells. Am J Physiol Heart Circ Physiol 292:2(H954-62)2007 Feb
16754746. Yang B, Oo TN, Rizzo V, Lipid rafts mediate H2O2 prosurvival effects in cultured endothelial cells. FASEB J 20:9(1501-3)2006 Jul
15471980. Radel C, Rizzo V, Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization. Am J Physiol Heart Circ Physiol 288:2(H936-45)2005 Feb
14644772. Ferraro JT, Daneshmand M, Bizios R, Rizzo V, Depletion of plasma membrane cholesterol dampens hydrostatic pressure and shear stress-induced mechanotransduction pathways in osteoblast cultures. Am J Physiol Cell Physiol 286:4(C831-9)2004 Apr
12816751. Rizzo V, Morton C, DePaola N, Schnitzer JE, Davies PF, Recruitment of endothelial caveolae into mechanotransduction pathways by flow conditioning in vitro. Am J Physiol Heart Circ Physiol 285:4(H1720-9)2003 Oct
12807699. Gertzberg N, Neumann P, Rizzo V, Johnson A, NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-alpha. Am J Physiol Lung Cell Mol Physiol 286:1(L37-48)2004 Jan
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