Up-regulation of AT1 and AT2 receptors in postinfarcted hypertrophied myocytes and stretch-mediated apoptotic cell death

A. Leri, Y. Liu, B. Li, F. Fiordaliso, A. Malhotra, R. Latini, J. Kajstura, P. Anversa

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To determine whether up-regulation of AT1 and AT2 receptors occurred in hypertrophied myocytes after infarction and whether AT2 played a role in stretch-mediated apoptosis, left ventricular myocytes were dissociated from the surviving portion of the wall 8 days after coronary occlusion and cardiac failure in rats. Control cells were obtained from sham-operated animals. Myocytes were stretched in an equibiaxial stretch apparatus and angiotensin II (Aug II) formation and cell death were measured 3 and 12 hours later. AT1 and AT2 proteins were evaluated in freshly isolated myocytes and after stretch. The effects of AT1 and AT2 antagonists on stretch-induced Aug II synthesis and apoptosis were also established. Myocardial infarction increased AT1 and ATe in myocytes and stretch further up-regulated these receptors. Ang II levels were higher in postinfarcted myocytes and this peptide increased with the duration of stretch in both groups of cells. Similarly, apoptosis increased with time in control and postinfarcted myocytes. Absolute values of Ang II and apoptosis were greater in myocytes from infarcted hearts at 3 and 12 hours after stretch. Addition of AT1 blocker to cultures inhibited stretch-activated apoptosis in both myocyte populations as well as the generation of Ang II in postinfarcted myocytes. In contrast, AT2 antagonists had no impact on these cellular events. In conclusion, Ang II stimulated cell death through AT1 receptor activation, whereas ligand binding to ATe receptor did not alter Ang II concentration and apoptosis in normal and postinfarcted hypertrophied myocytes.

Original languageEnglish
Pages (from-to)1663-1672
Number of pages10
JournalAmerican Journal of Pathology
Issue number5
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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