The scar neovasculature after myocardial infarction in rats.
A series of novel techniques, adapted from the field of tumor biology, were developed to quantify vascular structure and function and to explore the role of ANG II receptor AT1 in cardiac remodeling after myocardial infarction (MI). We examined the scar neovasculature at 1-4 wk post-MI in Sprague-Dawley rats with a view toward its ability to deliver and exchange oxygen. CD31 and DiOC7(3) staining was used to visualize anatomical vessels vs. those perfused. EF5/Cy3 immunohistochemical staining was used to quantify tissue hypoxia. We compared untreated controls with rats treated with losartan, an AT1 receptor antagonist. Our findings indicated that, at the infarct site, there was not only a 42-75% (1-4 wk post-MI) decrease in the number of anatomical vessels compared with controls but also a decrease in the fraction of perfused vessels from 70% in normal coronary vasculature to 48% at the infarct site. These changes were accompanied by progressive increases in diffusion distance and tissue hypoxia (100% increase in EF5/Cy3 staining at 4 wk post-MI). Losartan-treated rats exhibited a significantly less marked reduction in vascular perfusion and a significantly lesser extent of tissue hypoxia. Over the course of 4 wk post-MI, there is a reduction in coronary vasculature at the infarct site, the extent of which is attenuated by losartan. These findings implicate AT1 receptor upregulation, and perhaps angiotensin-related peptides, as being antiangiogenic.
Wang
Bin
B
Dept. of Mechanical Engineering, 1947 North 12th St., Philadelphia, PA 19122, USA.
Ansari
Ramin
R
Sun
Yao
Y
Postlethwaite
Arnold E
AE
Weber
Karl T
KT
Kiani
Mohammad F
MF
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002921:Cicatrix / Q000150:complications* / Q000209:etiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan