Abstract 14748: Protective Role of Cardiac-Specific alpha1A-AR Overexpression in Chronic Myocardial Infarction Through Improved Blood Flow
Relatively few transgenic (TG) cardiomyocyte (CM)-specific overexpression models reduce infarct size and afford protection from chronic permanent coronary artery occlusion (CAO). This is because, in the absence of collateral blood flow or angiogenesis, it is unlikely that infarct size would be reduced following permanent CAO, given that transgene overexpression is CM specific and does not occur in blood vessels. The goal of this investigation was to determine if the α1A-adrenergic receptor (AR) protects against permanent CAO-induced chronic ischemia and to elucidate the underlying mechanisms in α1A-TG rats with CM-specific receptor overexpression. Four weeks after permanent left anterior descending CAO, LV ejection fraction was greater, p<0.05, in α1A-TG rats (55±3.6%) than in non-TG littermates (NTLs) (35±3.1%), whereas LV systolic wall stress was lower, p<0.05, in TGs than NTLs (122±15 vs. 240±19 Kdyn/cm2). In addition, our hypothesis was that there was improved blood flow to the ischemic zone, which would diminish the scar by providing more blood flow. Indeed, at 1 week after permanent CAO, there was more viable tissue within the risk area, assessed by picrosirius red staining (34±1.8 vs. 17±1.8%, p<0.05) compared to NTLs. Using colored microspheres, coronary blood flow within the ischemic zone was significantly higher in TG than that in NTL (0.95±0.09 vs. 0.19±0.11 ml/min/g, p<0.05). At 4 weeks, fibrosis, reported as percent of myocardium in the adjacent area, was less in TG (15±0.3%) than in NTLs (21±0.6%). Thus, a transgenic model of CM-specific α1A-overexpression shows protection from chronic permanent CAO, which is due to an enhanced coronary circulation that maintains blood flow within the area at risk better than in NTLs, resulting in improved cardiac performance.
- © 2013 by American Heart Association, Inc.