Reactive oxygen species are critical mediators of coronary collateral development in a canine model.
Recent evidence suggests that reactive oxygen species (ROS) promote proliferation and migration of vascular smooth muscle (VSMC) and endothelial cells (EC). We tested the hypothesis that ROS serve as crucial messengers during coronary collateral development. Dogs were subjected to brief (2 min), repetitive coronary artery occlusions (1/h, 8/day, 21 day duration) in the absence (occlusion, n = 8) or presence of N-acetylcysteine (NAC) (occlusion + NAC, n = 8). A sham group (n = 8) was instrumented identically but received no occlusions. In separate experiments, ROS generation after a single 2-min coronary artery occlusion was assessed with dihydroethidium fluorescence. Coronary collateral blood flow (expressed as a percentage of normal zone flow) was significantly increased (71 +/- 7%) in occlusion dogs after 21 days but remained unchanged (13 +/- 3%) in sham dogs. Treatment with NAC attenuated increases in collateral blood flow (28 +/- 8%). Brief coronary artery occlusion and reperfusion caused ROS production (256 +/- 33% of baseline values), which was abolished with NAC (104 +/- 12%). Myocardial interstitial fluid produced tube formation and proliferation of VSMC and EC in occlusion but not in NAC-treated or sham dogs. The results indicate that ROS are critical for the development of the coronary collateral circulation.
Gu
Weidong
W
Department of Anesthesiology, Medical College of Wisconsin, 8701 Water-town Plank Road, Milwaukee, WI 53226, USA.
Weihrauch
Dorothee
D
Tanaka
Katsuya
K
Tessmer
John P
JP
Pagel
Paul S
PS
Kersten
Judy R
JR
Chilian
William M
WM
Warltier
David C
DC
D000818:Animals; D002455:Cell Division; D003097:Collateral Circulation; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D005110:Extracellular Space / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D009389:Neovascularization, Pathologic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors