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Endothelial mechanotransduction with loss of shear is a signal for angiogenesis
Author(s) -
Chatterjee Shampa,
Hong NanKang,
Yu Kevin,
Fisher Aron B
Publication year - 2010
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.24.1_supplement.602.3
Subject(s) - angiogenesis , cd31 , nadph oxidase , arteriogenesis , neovascularization , ischemia , vascular endothelial growth factor , chemistry , microbiology and biotechnology , reactive oxygen species , medicine , biology , vegf receptors
We have reported earlier that ischemia in the pulmonary vasculature results in reactive oxygen species (ROS) generation due to KATP channel closure that leads to NADPH oxidase activation. Here we found that pulmonary endothelial cells respond to ischemia in vitro, by increasing their angiogenic potential as compared to cells in static culture. We also investigated ischemia in the vasculature in vivo by femoral artery ligation. Angiogenesis (neovascularization) was assessed by visualization of fluorescence microbeads in the ischemic tissue following their injection into tail vein of mice. Neovascularization observed in wild type mice at 5 days after ligation was significantly decreased in mice that were null for KATP channel, gp91phox subunit of NADPH oxidase or Akt1. Pulmonary microvascular endothelial cells and lungs isolated from these knockout mice do not produce ROS with ischemia. The ischemic tissues from wild type were analyzed for vascular endothelial growth factor (VEGF). Wild type mice showed increased expression of VEGF with ischemia which was not observed in KATP channel, gp91phox and Akt null mice. We conclude that ROS generated with endothelial mechanotransduction causes angiogenesis via increased VEGF expression. ROS thus represents an attempt at neovascularization to restore the impeded blood flow.