Development of murine ischemic cardiomyopathy is associated with a transient inflammatory reaction and depends on reactive oxygen species

Oliver Dewald, Nikolaos G. Frangogiannis, Martin Zoerlein, Georg D. Duerr, Christina Klemm, Pascal Knuefermann, George Taffet, Lloyd H. Michael, James D. Crapo, Armin Welz, Mark L. Entman

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

We examined the effects of daily repetitive brief (15 min) myocardial ischemia and reperfusion (I/R) in WT C57/BL6 and extracellular superoxide dismutase (EC-SOD)-overexpressing mice. In the absence of myocardial necrosis, I/R resulted in persistent fibrosis in ischemic areas of C57/BL6 mice associated with persistent global and segmental anterior wall dysfunction. The I/R protocol induced chemokines (peak 3 days) followed sequentially by infiltration of macrophages and myofibroblasts (5 days). Fibrosis peaked at 7 days and was stable at 28 days despite regression of the chemokine and cellular response. Discontinuation of I/R at 7 or 28 days led to regression of fibrosis and ventricular dysfunction. In contrast, the EC-SOD mice developed markedly less chemokine induction, cell response, and fibrosis, with no ventricular dysfunction. Reversible fibrosis and ventricular dysfunction are features of human hibernating myocardium. The reduction of the cellular and functional response in EC-SOD mice suggests a role for reactive 02 in the pathogenesis of ischemic cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)2700-2705
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number5
DOIs
StatePublished - Mar 4 2003
Externally publishedYes

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