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ROS generated with Ischemia are a Redox Signal for Angiogenesis
Author(s) -
Chatterjee Shampa,
Hong NanKang,
Yu Kevin,
Fisher Aron
Publication year - 2009
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.23.1_supplement.1007.4
Subject(s) - nadph oxidase , angiogenesis , ischemia , reactive oxygen species , neovascularization , matrigel , chemistry , microbiology and biotechnology , in vivo , biology , medicine , cancer research
We have reported earlier that ischemia in the pulmonary vasculature results in reactive oxygen species (ROS) generation due to closure of a K ATP channel leading to endothelial NADPH oxidase activation. Here, we investigated the effect of ischemic ROS on the angiogenic potential of endothelial cells in vitro and in vivo. Flow adapted ischemic mouse pulmonary microvascular endothelial cells (PMVEC) (72 h flow adaptation, 1 h ischemia) injected into a matrigel matrix showed ~4 fold higher tube formation than static cells. Tube formation was not detected in PMVEC derived from mice with knockout of K ATP channels or gp91 phox subunit of NADPH oxidase. (These null cells do not generate ROS with ischemia). Tube formation in static cells could be increased by the addition of exogenous ROS but flow adapted cells were unaffected. Using an in vivo model, ischemia (femoral artery ligation) resulted in neovascularization as ascertained by microscopic evaluation in wild type mice but was significantly decreased in mice with knockout of K ATP channel or the gp91 phox subunit of NADPH oxidase. Increased VEGF expression was observed in ischemic tissue of wild type mice and was abolished in K ATP channel and gp91phox null mice. We conclude that ROS with ischemia serves as a signal for angiogenesis and that the ROS triggered VEGF formation represents an attempt at neovascularization to restore the impeded blood flow.