gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Divergent role of AT1 and AT2 receptors in myocardial ischemia-induced apoptosis and inflammation

Meeting Abstract (Hypertonie 2004)

  • J. Li - Center for Cardiovascular Research (CCR)/ (Berlin, D)
  • E. Kaschina - Center for Cardiovascular Research (CCR)/ (Berlin, D)
  • K. Elkhrbash - Center for Cardiovascular Research (CCR)/ (Berlin, D)
  • M. Timm - Center for Cardiovascular Research (CCR)/ (Berlin, D)
  • M. Sommerfeld - Center for Cardiovascular Research (CCR)/ (Berlin, D)
  • T. Unger - Center for Cardiovascular Research (CCR)/ (Berlin, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP13

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch013.shtml

Veröffentlicht: 10. August 2005

© 2005 Li et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Previous studies have revealed that cardiac angiotensin receptors, including AT1 and AT2 subtypes, are upregulated after myocardial infarction (MI). In addition, we have previously shown that the number of cardiomyocytes that express the AT1 and AT2 receptor mRNA is not increased in the noninfarcted myocardium (remote from the infarction). The cell sources of these upregulated angiotensin receptors and their potential relevance in myocardial ischemia-induced apoptosis and inflammation are not yet defined. Cardiac apoptosis and inflammation were characterized by evaluating cardiac expression of apoptotic markers such as p53, Bax and caspase-3 and anti-inflammatory cytokine IL-10, respectively, using Western Blot / immunohistochemistry analysis. Seven days after experimental MI in rats, cardiac p53, Bax, caspase-3 and IL-10 were significantly upregulated. Multiple immunofluorescence labeling demonstrated that both increased AT1 receptor and p53 were colocalized in cardiomyocytes (alpha-sarcomeric actin+) in the border-zone of the infarction whereas AT2 receptor and IL-10 were mainly co-expressed in infiltrated macrophages (ED1+) in the area between the border-zone and necrosis. Blocking AT1 receptors via valsartan dramatically suppressed the cardiac expression of apoptotic markers including p53, Bax and caspase-3 but enhanced the expression of IL-10, whereas blocking AT2 receptors via PD 123319 failed to influence the expression of theses apoptotic markers, but PD 123319 significantly attenuated the cardiac expression of IL-10. These results suggest a divergent role of AT1 and AT2 receptors in myocardial ischemia-induced apoptosis and inflammation. AT1 receptors may initiate cardiomyocyte apoptosis by inducing p53-triggered apoptotic cascade whereas AT2 receptors may exert an anti-inflammatory effect by mediating cardiac IL-10 expression in infiltrated macrophages.