Abstract 4378: Apoptosis in Heart Failure Predominantly Involves Non-Myocytes
Apoptosis has been considered a cardinal sign of heart failure (HF) and a major factor in its pathogenesis. If the loss of myocytes contributes to the development of HF, it is assumed that the apoptosis occurs in cardiomyocytes, which reside in otherwise viable tissue in myocardium adjacent and remote to the infarct. We tested this hypothesis in a non-human primate model of chronic HF induced by rapid pacing, 2–3 months following myocardial infarction (MI). Left ventricular (LV) ejection fraction decreased in MI (from 75±6.2 to 56±5.2%, p<0.05) and further, p<0.05, in HF (27.8±2.8%). Apoptosis was assessed by TUNEL and by caspase-3 cleavage. As expected, apoptosis increased in MI, p<0.05, and further, p<0.05, when HF developed, and was greater in adjacent than remote myocardium (Table 1⇓). In order to discriminate apoptosis in non-myocytes and myocytes, the myocardium was stained with cleaved caspase-3, and counterstained with rhodamine-conjugated wheat germ agglutinin (WGA) or with troponin-I, a cardiac muscle marker. The ventricular myocytes were stained by WGA at the outer membrane and across in a striated pattern as associated with the T tubule network. Surprisingly, the majority of apoptotic cells in MI and MI+HF and in both adjacent and remote areas were non-myocytes (Table 1⇓). For characterization of types of non-myocytes, serial tissue sections were immunostained with antibodies recognizing macrophages (HAM56), neutrophils (elastase NP57), and endothelial cells (CD31). Macrophages were the cell type contributing the largest fraction of apoptotic non-myocytes (47%). In conclusion, HF does induce apoptosis in the heart, but it occurs predominantly in non-myocytes, suggesting that the role of apoptosis in the pathogenesis of HF may not simply be due to simple loss of myocyte contractile elements.