Ongoing or Completed During the Last 3 Years:
"Mechanisms of vascular permeability in diabetes: Role of peroxynitrite in VEGF/permeability signaling pathway"
Type: Post-doctoral Fellowship.
Agency: American Heart Association, Southeast Affiliate
Period: July 1, 2002 to June 30, 2004.
The goal is to elucidate the signaling pathway underlying retinal vascular permeability increases in diabetes and to define the role of reactive nitrogen species in the process.
"Molecular Mechanisms of VEGF's angiogenic pathway: Role of Peroxynitrite"
Agency: American Heart Association, National
Type: Scientist Development Grant.
Principle Investigator: Azza B. El-Remessy
Period: January1, 2005 to December 31, 2008.
Total Award: $250,000. Effort: 40 %
The goal is to elucidate the role of peroxynitrite as a novel transducer of VEGF's angiogenic signaling pathways and function in microvascular endothelial cells.
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1996-1998 Predoctoral fellowship from Egyptian Cultural Bureau.
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2000 - 2001 Postdoctoral fellowship award from ARVO/Novartis Inc.
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2002 - 2002 Young Scientist Travel award from ASPET, American Society of Pharmacology & Experimental Therapeutics.
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2002- 2004 Postdoctoral fellowship award from American Heart Association, Southeast.
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2004 Young Investigator Travel Award from National Eye Institute.
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2005-2008 Scientist Development Grant from AHA/National.
El-Remessy, A.B., Behzadian, M.A., Abou-Mohamed, G. Franklin, T., Caldwell, R.W., Caldwell, R.B. Peroxyntitrite increases vascular permeability in experimental diabetes by a mechanism involving increased expression of VEGF and urokinase plasminogen activator receptor (uPAR). Am.J Pathol, 162:1995-2004, 2003.
El-Remessy, A.B., Abou-Mohamed, G., Caldwell, R.W., Caldwell, R.B., High glucose increases tyrosine nitration and superoxide anion formation in endothelial cells: Role of eNOS uncoupling and aldose reductase activation. Invest Ophthalmol Vis Sci, 44:3135-43, 2003.
El-Remessy, A.B. Khalil, I. Abou-Mohamed, G. Matragoon, S. Caldwell, R.B., Caldwell, R.W., and Liou, G.I. Neuroprotective effect of delta 9-tetrahydrocannabinol and cannabidiol in NMDA-induced retinal neurotoxicity: involvement of peroxynitrite. Am J Pathol, 162:1995-2004, 2003
Gu, X., El-Remessy, A.B., Brooks, S.E., Al-Shabrawey, M., Tsai, N.T., Caldwell, R.B. Hyperoxia induces retinal vascular endothelial cell apoptosis through formation of peroxynitrite. Am J Physiol Cell Physiol, 285:C546-54, 2003.
Al-Shabrawey, M. El-Remessy, A.B., Gu, X., Brooks, S.E., S. Hamed, M.S., Huang, P., Caldwell, R.B. Normal vascular development in mice deficient in endothelial NO synthase: Possible role of neuronal NO synthase, Mol.Vis. 9:549-558, 2003.
Caldwell, R.B., Bartoli, M., Behzadian, M.A., El-Remessy, A.B., Al-Shabrawey, M, Platt, D.H., Caldwell, R.W. Vascular endothelial growth factor and diabetic retinopathy: Pathophysiological mechanisms and treatment perspectives. Diabetes Metabolism Research Reviews, 19:442-455, 2003.
Abou-Mohamed, G., Johnson, J., Jin, L., El-Remessy, A.B., Kaesemeyer, W., Caldwell, R.B., Caldwell, R.W. Roles of superoxide, peroxynitrite and protein kinase C in the development of tolerence to nitroglycerin. J. Pharmacol. & Exp.Therap. 308:289-299, 2004.
El-Remessy, A.B., Bartoli, M., Platt, D.H., Fulton, D. and Caldwell R.B. High glucose inactivates VEGF survival signaling in retinal endothelial cells via PI-3 kinase nitration. J. Cell Science 118:243-52, 2005
Platt, D.H. Bartoli, M., El-Remessy, A.B., Fulton, D. and Caldwell, R.B.. Peroxynitrite-mediated activation of VEGF Transcription in Vascular cells via signal transducer and activator of transcription-3. Free Rad. Biol. Med, 39: 1353-1361, 2005
Al-Shabrawey, M. Bartoli, M. Platt. D.H., El-Remessy, A.B., Behzadien, M.A., Matragoon, S., Caldwell, R.W. and Caldwell, R.B. Inhibition of NADPH oxidase block retinal neovascularization in oxygen-induced retinopathy. Am. J. Pathol, 167:599-607, 2005
El-Remessy, A.B. , Al-Shabrawey,M., Khalifa, Y., Caldwell, R.B., and Liou, G.I. Neuroprotective and blood-retina barrier preserving effects of cannabidiol on experimental diabetes. Am. J. Pathol. 168: 235-244, 2006
Bartoli, M., Platt, D.H., Lemtalsi, T., El-Remessy, A.B., Marrero, M. and Caldwell, R.B. High glucose-induced oxidative stress modifies VEGF-dependent STAT3 activation. Free Rad. Biol. Med,in revision
EI-Remessy, A.B., Al-Shabrawey, M., Platt, D.H., Bartoli, M., Ghaly, N., Behzadian, M.A., Motamed, K. and Caldwell, R.B. Peroxynitrite mediates VEGF's angiogenic signaling via nitration-independent mechanism. (JCS, submitted)
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