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Reactive Oxygen Species (ROS) generated with obstruction of blood flow drives vascular remodeling
Author(s) -
Browning Elizabeth Anne,
Hong Nankang,
Fisher Aron B.,
Chatterjee Shampa
Publication year - 2011
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.25.1_supplement.1093.3
Subject(s) - reactive oxygen species , nadph oxidase , angiogenesis , chemistry , arteriogenesis , cd31 , ligation , vasodilation , apocynin , mitochondrial ros , microbiology and biotechnology , medicine , biology , biochemistry
We have shown previously that in intact lung or isolated cells, stop of flow mimicking a pulmonary vascular obstruction results in endothelial production of ROS mediated via K ATP channel closure, cell membrane depolarization, and activation of endothelial NADPH oxidase (NOX2). This ROS was found to drive endothelial cell proliferation in vitro . We thus hypothesized that ROS generated by the vascular endothelium upon obstruction of flow in vivo regulates remodeling of blood vessels and/or angiogenesis and investigated this link using a murine femoral artery ligation model. There was extensive vascular remodeling (as assessed by ultrasound imaging and post‐mortem visualization of fluorescent microbeads in the post‐ligated tissue) in wild type (WT) but low to no remodeling in mice that do not produce ROS (K ATP channel or NOX2 null). ROS generation and lipid peroxidation (as measured by dihydroethidium staining and TBARS assay) were increased at 1 hr post ligation in WT mice. Low vascular remodeling also was observed in L‐NAME‐fed WT mouse. NO levels as detected by nitrite, nitrate, and S‐nitrosothiol assays were found to be higher in ligated limb of NOX2 null as compared to WT mice indicating greater NO bioavailability. These results indicate that both ROS and NO are required for revascularization in the ischemic mouse hind limb model. NHLBI‐T32‐S54932