Journal
NEW ENGLAND JOURNAL OF MEDICINE
Volume 344, Issue 23, Pages 1750-1757Publisher
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJM200106073442303
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- NHLBI NIH HHS [HL-39902, HL-38132, HL-43023] Funding Source: Medline
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Background The scarring of the heart that results from myocardial infarction has been interpreted as evidence that the heart is composed of myocytes that are unable to divide. However, recent observations have provided evidence of proliferation of myocytes in the adult heart. Therefore, we studied the extent of mitosis among myocytes after myocardial infarction in humans. Methods Samples from the border of the infarct and from areas of the myocardium distant from the infarct were obtained from 13 patients who had died 4 to 12 days after infarction. Ten normal hearts were used as controls. Myocytes that had entered the cell cycle in preparation for cell division were measured by labeling of the nuclear antigen Ki-67, which is associated with cell division. The fraction of myocyte nuclei that were undergoing mitosis was determined, and the mitotic index (the ratio of the number of nuclei undergoing mitosis to the number not undergoing mitosis) was calculated. The presence of mitotic spindles, contractile rings, karyokinesis, and cytokinesis was also recorded. Results In the infarcted hearts, Ki-67 expression was detected in 4 percent of myocyte nuclei in the regions adjacent to the infarcts and in 1 percent of those in regions distant from the infarcts. The reentry of myocytes into the cell cycle resulted in mitotic indexes of 0.08 percent and 0.33 percent, respectively, in the zones adjacent to and distant from the infarcts. Events characteristic of cell division - the formation of the mitotic spindles, the formation of contractile rings, karyokinesis, and cytokinesis - were identified; these features demonstrated that there was myocyte proliferation after myocardial infarction. Conclusions Our results challenge the dogma that the adult heart is a postmitotic organ and raise the possibility that the regeneration of myocytes may contribute to the increase in muscle mass of the myocardium. (N Engl J Med 2001;344:1750-7.) Copyright (C) 2001 Massachusetts Medical Society.
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