Reactive oxygen species promote angiogenesis in the infarcted rat heart.
The purpose of this study was to determine whether reactive oxygen species (ROS) promote cardiac angiogenesis following myocardial infarction (MI) and contribute to cardiac repair. Rats with MI were treated with or without antioxidants, tempol and apocynin. Hearts of these rats were collected at days 2, 4, 7 and 14 post-MI. We examined the spatial and temporal relationship between oxidative stress and angiogenesis as well as the potential regulation of ROS in cardiac angiogenesis. We found: (i) following MI, gp91(phox), a subunit of NADPH oxidase, a key enzyme for ROS production, was significantly increased in the border zone at day 2, followed by the infarcted myocardium at day 4, peaked at day 7 and declined at day 14, while superoxide dismutase was significantly reduced; (ii) malondialdehyde, a marker of oxidative stress, was significantly increased in the infarcted myocardium at day 7; (iii) pre-existing blood vessels in the infarcted myocardium underwent necrosis post-MI, whereas newly formed vessels appeared at the border zone at day 4, and then extended into the infarcted myocardium, where microvascular density peaked at day 7 and (iv) antioxidant treatment significantly reduced microvascular density in the infarcted myocardium at day 7. These observations suggest that following MI, angiogenesis is mostly active in the infarcted myocardium in the first week, which is temporally and spatially coincident with enhanced ROS. Suppression of angiogenesis by antioxidants indicates that ROS promote angiogenesis in the infarcted myocardium and contribute to cardiac repair. Further studies are required to determine the mechanisms responsible for ROS-mediated cardiac angiogenesis.
Zhao
Wenyuan
W
Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, Memphis, TN 38163, USA.
Zhao
Tieqiang
T
Chen
Yuanjian
Y
Ahokas
Robert A
RA
Sun
Yao
Y
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000503:physiopathology*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000098:Acetophenones; D000975:Antioxidants; D003497:Cyclic N-Oxides; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; D013113:Spin Labels; C056165:acetovanillone; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C001803:tempol