Increased angiogenesis as a mechanism for the preserved cardiac function in rats with chronic pressure overload

Abstract

Reduced coronary reserve and left ventricular (LV) function are hallmarks of chronic pressure overload. In rats with 4–8 wks of transverse aortic constriction (TAC), the LV/aortic pressure gradient (145±7mmHg), was greater than that observed in most other models of TAC, but LV systolic wall stress was not significantly increased and LV ejection fraction, measured by echocardiography, was not decreased, but actually was enhanced, p<0.05, compared with sham rats at 8 wks (79±3% vs. 73±1%). Coronary reserve, the increase in coronary flow velocity with adenosine measured echocardiographically, which is depressed in almost all models of LV hypertrophy, was preserved in TAC rats vs. sham. There was a significant increase, p<0.05, in vascular endothelial growth factor (VEGF), measured by western blotting (11.9 vs. sham 3.3) and there were increased, p<0.05, Ki67 positive endothelial cells in TAC rats (22±3 Ki67 positive/mm2) vs. sham (12±2 Ki67 positive/mm2), indicative of angiogenesis. Capillary density, quantified microscopically with isolectin staining, was also increased in TAC (480 units/mm2) vs. sham (397 units/mm2). Thus, this unusual model of chronic pressure overload LV hypertrophy in the rat demonstrated enhanced LV function and preserved coronary reserve, which in turn could be attributed to the increased angiogenesis.