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Ischemia in the Pulmonary Vasculature: Redox Signaling for Angiogenesis
Author(s) -
Chatterjee Shampa,
Hong Nankang,
Fisher Aron B.
Publication year - 2008
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.22.1_supplement.929.1
Subject(s) - matrigel , angiogenesis , ischemia , neovascularization , microbiology and biotechnology , in vivo , endothelial stem cell , pathology , biology , chemistry , in vitro , medicine , cancer research , biochemistry
We have reported earlier that ischemia in the pulmonary vasculature results in reactive oxygen species (ROS) generation. In in vitro experiments using pulmonary microvascular endothelial cells (PMVEC), this post ischemic ROS was found to cause increased endothelial cell proliferation. We hypothesized that this proliferation is an angiogenic response of the endothelium. Here we investigated the angiogenic potential of flow adapted ischemic PMVEC (72 h flow adaptation, 1 h ischemia) as compared to static cells using in vitro and in vivo angiogenic assays. In matrigel dishes, flow adapted ischemic PMVEC showed ~4 fold higher tube formation than static cells. In the matrigel plug assay, where cells mixed in matrigel were implanted as a plug subcutaneously into nude mice, ischemic cells showed more extensive appearance of new vessels and endothelial markers as compared to static cells. Hind limb ischemia in wild type mice and mice with knockout of gp91phox (the membrane component of the NADPH oxidase) was used to study angiogenesis in vivo. Five days post ischemia, the growth of new vessels as ascertained by microscopic evaluation of the ischemic tissue was lower in gp91phox knockout mice where ROS generation was compromised. We thus conclude that the ROS‐dependent proliferation with ischemia is an angiogenic signal and represents an attempt at neovascularization to restore the impeded blood flow.