Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53

Shani Bialik, David L. Geenen, Isaac E. Sasson, Rendi Cheng, James W. Horner, Sydney M. Evans, Edith M. Lord, Cameron J. Koch, Richard N. Kitsis

Research output: Contribution to journalArticle

326 Citations (Scopus)

Abstract

Significant numbers of myocytes die by apoptosis during myocardial infarction. The molecular mechanism of this process, however, remains largely unexplored. To facilitate a molecular genetic analysis, we have developed a model of ischemia-induced cardiac myocyte apoptosis in the mouse. Surgical occlusion of the left coronary artery results in apoptosis as indicated by the presence of nucleosome ladders and in situ DNA strand breaks. Apoptosis occurs mainly in cardiac myocytes, and is shown for the first time to be limited to hypoxic regions during acute infarction. Since hypoxia-induced apoptosis in other cell types is dependent on p53, and p53 is induced by hypoxia in cardiac myocytes, we investigated the necessity of p53 for myocyte apoptosis during myocardial infarction. Myocyte apoptosis occurs as readily however, in the hearts of mice nullizygous for p53 as in wild-type littermates. These data demonstrate the existence of a p53-independent pathway that mediates myocyte apoptosis during myocardial infarction.

Original languageEnglish (US)
Pages (from-to)1363-1372
Number of pages10
JournalJournal of Clinical Investigation
Volume100
Issue number6
StatePublished - Sep 15 1997

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Muscle Cells
Myocardial Infarction
Apoptosis
Cardiac Myocytes
DNA Breaks
Nucleosomes
Infarction
Molecular Biology
Coronary Vessels
Ischemia

Keywords

  • Ischemic heart disease
  • Knock- out mice
  • Molecular genetics
  • Nitroimidazoles
  • Programmed cell death

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53. / Bialik, Shani; Geenen, David L.; Sasson, Isaac E.; Cheng, Rendi; Horner, James W.; Evans, Sydney M.; Lord, Edith M.; Koch, Cameron J.; Kitsis, Richard N.

In: Journal of Clinical Investigation, Vol. 100, No. 6, 15.09.1997, p. 1363-1372.

Research output: Contribution to journalArticle

Bialik, S, Geenen, DL, Sasson, IE, Cheng, R, Horner, JW, Evans, SM, Lord, EM, Koch, CJ & Kitsis, RN 1997, 'Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53', Journal of Clinical Investigation, vol. 100, no. 6, pp. 1363-1372.
Bialik, Shani ; Geenen, David L. ; Sasson, Isaac E. ; Cheng, Rendi ; Horner, James W. ; Evans, Sydney M. ; Lord, Edith M. ; Koch, Cameron J. ; Kitsis, Richard N. / Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 6. pp. 1363-1372.
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AU - Horner, James W.

AU - Evans, Sydney M.

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AB - Significant numbers of myocytes die by apoptosis during myocardial infarction. The molecular mechanism of this process, however, remains largely unexplored. To facilitate a molecular genetic analysis, we have developed a model of ischemia-induced cardiac myocyte apoptosis in the mouse. Surgical occlusion of the left coronary artery results in apoptosis as indicated by the presence of nucleosome ladders and in situ DNA strand breaks. Apoptosis occurs mainly in cardiac myocytes, and is shown for the first time to be limited to hypoxic regions during acute infarction. Since hypoxia-induced apoptosis in other cell types is dependent on p53, and p53 is induced by hypoxia in cardiac myocytes, we investigated the necessity of p53 for myocyte apoptosis during myocardial infarction. Myocyte apoptosis occurs as readily however, in the hearts of mice nullizygous for p53 as in wild-type littermates. These data demonstrate the existence of a p53-independent pathway that mediates myocyte apoptosis during myocardial infarction.

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