Serum pigment epithelium-derived factor levels are independently associated with decreased number of circulating endothelial progenitor cells in healthy non-smokers

Abstract

Pigment epithelium-derived factor (PEDF), a glycoprotein that belongs to the superfamily of serine protease inhibitors, was first purified from conditioned medium of human retinal pigment epithelial cells with a potent neuronal differentiating activity [ [1] Tombran-Tink J. Chader C.G. Johnson L.V. PEDF: pigment epithelium-derived factor with potent neuronal differentiative activity. Exp Eye Res. 1991; 53: 411-414 Google Scholar ]. Recently, PEDF has been shown to be the most potent inhibitor of angiogenesis in the mammalian eye [ 2 Dawson D.W. Volpert O.V. Gillis P. et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. 1999; 285: 245-248 Google Scholar , 3 Duh E.J. Yang H.S. Suzuma I. et al. Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth. Invest Ophthalmol Vis Sci. 2002; 43: 821-829 Google Scholar ]. Indeed, PEDF not only inhibits retinal endothelial cell growth and migration, but also suppresses ischemia-induced retinal neovascularization [ 2 Dawson D.W. Volpert O.V. Gillis P. et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. 1999; 285: 245-248 Google Scholar , 3 Duh E.J. Yang H.S. Suzuma I. et al. Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth. Invest Ophthalmol Vis Sci. 2002; 43: 821-829 Google Scholar ]. Moreover, we have found that PEDF prevents vascular remodeling after balloon angioplasty and improves cardiac function in a rat model of acute myocardial infarction [ 4 Nakamura K. Yamagishi S. Matsui T. et al. Pigment epithelium-derived factor inhibits neointimal hyperplasia after vascular injury by blocking NADPH oxidase-mediated reactive oxygen species generation. Am J Pathol. 2007; 170: 2159-2170 Google Scholar , 5 Ueda S. Yamagishi S. Matsui T. Jinnouchi Y. Imaizumi T. Administration of pigment epithelium-derived factor inhibits left ventricular remodeling and improves cardiac function in rats with acute myocardial infarction. Am J Pathol. 2011; 178: 591-598 Google Scholar ]. These observations suggest that PEDF may also exert beneficial effects on ischemic heart disease as well as atherosclerosis.