May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Carboxyethylpyrrole Protein Modifications Stimulate Angiogenesis.
Author Affiliations & Notes
  • B. Anand–Apte
    Ophthalmic Research, Cole Eye Inst/Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, OH
  • K. Renganathan
    Ophthalmic Research, Cole Eye Inst/Cleveland Clinic Foundation, Cleveland, OH
  • Q. Ebrahem
    Ophthalmic Research, Cole Eye Inst/Cleveland Clinic Foundation, Cleveland, OH
  • X. Gu
    Ophthalmic Research, Cole Eye Inst/Cleveland Clinic Foundation, Cleveland, OH
  • R.G. Salomon
    Chemistry, Case Western Reserve University, Cleveland, OH
  • J.W. Crabb
    Ophthalmic Research, Cole Eye Inst/Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, OH
  • Footnotes
    Commercial Relationships  B. Anand–Apte, None; K. Renganathan, None; Q. Ebrahem, None; X. Gu, None; R.G. Salomon, None; J.W. Crabb, None.
  • Footnotes
    Support  EY12109, EY06603, EY14239, GM21249,FFB, CCF
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 483. doi:
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      B. Anand–Apte, K. Renganathan, Q. Ebrahem, X. Gu, R.G. Salomon, J.W. Crabb; Carboxyethylpyrrole Protein Modifications Stimulate Angiogenesis. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):483.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Choroidal neovascularization (CNV) accounts for more than 80% of the severe debilitating vision loss in all age–related macular degeneration (AMD) yet the etiology is not known. Carboxyethylpyrrole (CEP) adducts are uniquely generated from oxidation of docosahexaenoate–containing lipids and are more abundant in AMD than normal Bruch’s membrane. We tested the hypothesis that CEP protein adducts stimulate angiogenesis and contribute to CNV in AMD. Methods: Human serum albumin (HSA) and Gly–Lys–dipeptide were chemically modified with 4,7–dioxoheptanoic acid (DOHA) to yield carboxyethylpyrrole–albumin (CEP–HSA). Pyrrole content was determined by the Erlich assay and protein was quantified by amino acid analysis. Human ARPE19 cells were treated in vitro with docosahexaenoate–phosphatidyl choline (DHA–PC) and CEP adduct formation was evaluated by Western analysis. In vivo angiogenic properties of CEP–HSA and CEP–Gly–Lys dipeptide were evaluated using the chick chorioallantoic membrane and rat corneal implant assays. Results: CEP immunoreactivity by Western analysis was maximal after 4–5 h in ARPE19 cells treated with 200 µM DHA–PC. Low picomole amounts of CEP–HSA and CEP–dipetide stimulated angiogenesis in vivo in the chorioallantoic membrane and corneal implant assays. Preliminary results support monoclonal anti–CEP neutralization of limbal vessel growth stimulated by CEP–HSA. Conclusions: CEP protein adducts stimulate angiogenesis and may play a role in CNV. This observation is consistent with results from others showing that oxidative protein modifications from carbohydrates (i.e., advanced glycation end products or AGEs) stimulate angiogenesis in vivo. Current efforts are focused upon determining whether CEP adducts stimulate angiogenesis via a VEGF independent pathway. Supported in part by NIH grants EY06603, EY14239, GM21249, a Research Center Grant from The Foundation Fighting Blindness and funds from the Cleveland Clinic Foundation.

Keywords: oxidation/oxidative or free radical damage • age–related macular degeneration • neovascularization 
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