Abstract
It is generally believed that chronic pressure overload increases myocyte apoptosis, and that the resultant loss of myocytes is responsible for the cardiac dysfunction. If this reasoning is correct, then protecting myocyte apoptosis with chronic pressure overload should increase numbers of myocytes. We examined the effects of protecting apoptosis by caspase inhibition (CI) with chronic pressure overload induced by thoracic aortic constriction (TAC). Left ventricular (LV) ejection fraction was reduced by TAC (55% vs 70%), but was protected with CI (66%). However, CI reduced myocyte apoptosis by only 0.06%, compared with non‐myocyte apoptosis (0.21%), and did not result in increased total myocyte number, which was similar in sham operated controls to TAC with and without CI. However, other mechanisms were potentially responsible for the protection of cardiac function: 1) CI reduced interstitial fibrosis (2.9%) compared to vehicle (6.8%) after TAC. 2) Ki67 staining of endothelial cells was increased with CI and TAC (3.4±0.7%) compared to vehicle group (1.4±0.6%) indicative of angiogenesis. 3) Ki67‐positive myocytes, indicative of myogenesis, were also higher with CI than vehicle (0.9±0.2% vs 0.3±0.1%). Thus, CI improved LV function after TAC, not by protecting myocyte apoptosis, but rather through angiogenesis and myogenesis, reducing myocardial fibrosis.
Published Version
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