[Ischemic heart disease and apoptosis].
In the last three years, apoptosis has been reported to be associated with cell death in ischemic heart diseases, for examples, acute ischemic cardiomyocyte death in acute myocardial infarction; death of the salvaged cardiomyocytes in old myocardial infarction; death of infiltrated leukocytes and granulation tissue cells after myocardial infarction. Apoptosis-related proteins such as Bcl-2, Bax and Fas are expressed in the salvaged cardiomyocytes edging the infarct area. In vitro experiment using cultured cardiomyocytes suggested hypoxia causes apoptosis in them. Thus, apoptosis may play important roles in ischemic heart diseases. For detecting apoptosis, however, all of the previous studies on acute ischemic cardiomyocyte death depended exclusively on DNA fragmentation (biochemical marker of apoptosis) by a DNA ladder on gel electrophoresis and in situ nick end labeling (TUNEL), but never documented the ultrastructural changes characteristic of apoptosis (morphological marker of apoptosis). Then, we examined the ultrastructure and DNA fragmentation of cardiomyocytes in rabbit myocardial infarction using electron microscopy combined with TUNEL (EM-TUNEL) which allows simultaneous observation of both markers in the same cell. Rabbits underwent 30-min ischemia followed by 0-, 30-min, 2-, 4- and 24-h reperfusion of a left coronary artery. In the infarcted tissue, EM-TUNEL revealed oncotic necrosis of cardiomyocytes with or without DNA fragmentation in the 2-h, 4-h, and 24-h reperfusion groups, but no apoptotic cardiomyocytes in ultrastructure in any groups. Thus, so-called apoptotic cardiomyocytes after ischemia/reperfusion may belong to a different category from apoptosis.
Takemura
G
G
Second Department of Internal Medicine, Gifu University School of Medicine.
Ohno
M
M
Fujiwara
H
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053938:DNA Fragmentation; D006801:Humans; D016252:Microscopy, Scanning Tunneling; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology; D011817:Rabbits