ROLE OF APOPTOSIS IN THE DISAPPEARANCE OF INFILTRATED AND PROLIFERATED INTERSTITIAL-CELLS AFTER MYOCARDIAL-INFARCTION

Myocardial infarction (MI) progresses from the acute death of myocytes and the infiltration of inflammatory cells into granulation, followed by scars. During the healing process, the myocardial interstitial cel l population in the infarcted tissues increases markedly and then decr eases. We postulated that apoptosis is responsible for this process. T wenty-four male Japanese white rabbits underwent a 30-minute occlusion of the left coronary artery followed by reperfusion for 2 days, 2 wee ks, or 4 weeks (n=8 each), The histological features consisted of dead cardiomyocytes and marked leukocyte infiltration at 2 days after MI a nd granulation consisting of numerous cu-smooth muscle actin-positive myofibroblasts, macrophage antigen-positive macrophages, and neovascul arization at 2 weeks. At 4 weeks, the cellularity decreased markedly, and scars were evident. Interstitial cells with positive nick end labe ling were significantly more frequent at the light microscopic level i n the 2-day MI samples (5.3+/-3.6% in the center and 6.9+/-3.3% in the periphery of the infarct region) than in the 2-week (2.5 +/- 1.0%) an d 4-week (0.5+/-0.5%) samples. DNA electrophoresis showed a clear ladd er in tissues from the ischemic areas at 2 days after MI but not at 2 and 4 weeks after MI. Ultrastructurally, typical apoptotic figures, in cluding apoptotic bodies and condensed nuclei without ruptured plasma membranes, were detected in leukocytes from all hearts with 2-day MI a nd in myofibroblasts, endothelial cells, and macrophages from all hear ts with 2-week MI. In the electron microscopic in situ nick end labeli ng, immunogold particles intensely labeled the condensed chromatin of the typical apoptotic nuclei. These particles were also accumulated on nuclei of the interstitial cells showing homogeneous density but not definite condensation as typical apoptotic nuclei, suggesting an early stage of apoptosis, Thus, apoptosis plays an important role in the di sappearance of both the infiltrated leukocytes and the proliferated in terstitial cells after MI. This finding may have therapeutic implicati ons for postinfarct ventricular remodeling through apoptosis handling during the healing stage of MI.