Transgenic mouse model of stunned myocardium.
Stunned myocardium is a syndrome of reversible contractile failure that frequently complicates coronary artery disease. Cardiac excitation is uncoupled from contraction at the level of the myofilaments. Selective proteolysis of the thin filament protein troponin I has been correlated with stunned myocardium. Here, transgenic mice expressing the major degradation product of troponin I (TnI1-193) in the heart were found to develop ventricular dilatation, diminished contractility, and reduced myofilament calcium responsiveness, recapitulating the phenotype of stunned myocardium. Proteolysis of troponin I also occurs in ischemic human cardiac muscle. Thus, troponin I proteolysis underlies the pathogenesis of a common acquired form of heart failure.
Murphy
A M
AM
Department of Pediatrics, Johns Hopkins University School of Medicine, Ross Building 1144, 720 Rutland Avenue, Baltimore, MD 21205, USA. murphy@jhmi.edu
Kögler
H
H
Georgakopoulos
D
D
McDonough
J L
JL
Kass
D A
DA
Van Eyk
J E
JE
Marbán
E
E
D008841:Actin Cytoskeleton / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000473:pathology; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D006339:Heart Rate; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D017682:Myocardial Stunning / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009210:Myofibrils / Q000378:metabolism; D019210:Troponin I / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left
D000318:Adrenergic beta-Agonists; D019210:Troponin I; D007545:Isoproterenol; D002118:Calcium