TY - JOUR
T1 - Development of murine ischemic cardiomyopathy is associated with a transient inflammatory reaction and depends on reactive oxygen species
AU - Dewald, Oliver
AU - Frangogiannis, Nikolaos G.
AU - Zoerlein, Martin
AU - Duerr, Georg D.
AU - Klemm, Christina
AU - Knuefermann, Pascal
AU - Taffet, George
AU - Michael, Lloyd H.
AU - Crapo, James D.
AU - Welz, Armin
AU - Entman, Mark L.
PY - 2003/3/4
Y1 - 2003/3/4
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0438035100
DO - 10.1073/pnas.0438035100
M3 - Article
C2 - 12586861
AN - SCOPUS:0037418276
VL - 100
SP - 2700
EP - 2705
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 5
ER -