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Attenuation of Retinal Neovascularization and Endothelial Cells Proangiogenic Activity in Endoglin Deficient Mice
Author(s) -
Park SunYoung,
Sorenson Christine M,
Sheibani Nader
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.48.2
Subject(s) - endoglin , angiogenesis , neovascularization , haploinsufficiency , retinal , matrigel , cancer research , microbiology and biotechnology , biology , phenotype , genetics , stem cell , biochemistry , cd34 , gene
Endoglin (Eng) is an auxiliary receptor for TGF‐β. TGF‐β regulates angiogenesis through balancing the pro‐proliferative and pro‐differentiation signaling pathways of endothelial cells (EC). However, the exact contribution of endoglin to TGF‐β activities, and more specifically, modulation of EC phenotype is unclear. Mutations in endoglin cause hereditary hemorrhagic telangiectasia‐1. Endoglin null mice fail to undergo proper vascular remodeling and maturation, and die early. Eng +/− mice exhibit some of the vascular defects seen in humans with endoglin haploinsufficiency. Here we show that haploinsufficiency of endoglin results in attenuation of retinal neovascularization during oxygen‐induced ischemic retinopathy. To gain detailed insight into the regulatory mechanisms which impact proangiogenic properties of EC, we prepared retinal EC from Eng+/+ and Eng+/− mice. Eng +/− retinal EC exhibited alterations in expression of EC markers including PECAM‐1, ICAM‐2, and VE‐cadherin. Eng +/− EC were less migratory and more adherent, and failed to undergo capillary morphogenesis in Matrigel. These changes were concomitant with decreased levels of eNOS and NO production. Eng +/− EC also proliferated at a faster rate and were less apoptotic. Together our results demonstrate an important autonomous role for endoglin expression in regulation of EC phenotype and angiogenesis. Supported by EY016695