Programmed myocyte cell death affects the viable myocardium after infarction in rats.
To determine whether apoptotic and necrotic myocyte cell death occur acutely and chronically after infarction, the formation of DNA strand breaks and the localization of myosin monoclonal antibody labeling were analyzed in the surviving myocardium from 20 min to 1 month. DNA strand breaks in myocyte nuclei were detected as early as 3 h following coronary artery occlusion and were still present at 1 month. This cellular process was characterized biochemically by internucleosomal DNA fragmentation which produced DNA laddering on agarose gel electrophoresis. Quantitatively, 155 myocyte nuclei per 10(6) cells exhibited DNA strand breaks in the portion adjacent to the infarcted tissue at 3-12 h. This parameter increased to 704 at 1-2 days and subsequently decreased to 364 at 7 days, 188 at 14 days, and 204 at 1 month. In the remote myocardium, the number of myocyte nuclei with DNA strand breaks was 84 per 10(6) at 3-12 h and remained essentially constant up to 1 month. Programmed myocyte cell death was accompanied by a decrease in the expression of bcl-2 and an increase in the expression of bax. The changes in the expression of these genes were present at 1 and 7 days after coronary artery occlusion. In conclusion, the mechanical load produced by myocardial infarction and ventricular failure may affect the regulation of bcl-2 and bax in the viable myocytes, triggering programmed cell death and the remodeling of the ventricular wall.
Cheng
W
W
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Kajstura
J
J
Nitahara
J A
JA
Li
B
B
Reiss
K
K
Liu
Y
Y
Clark
W A
WA
Krajewski
S
S
Reed
J C
JC
Olivetti
G
G
Anversa
P
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004249:DNA Damage; D006352:Heart Ventricles / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000166:cytology* / Q000473:pathology; D009218:Myosins / Q000032:analysis; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D009218:Myosins