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Science 21 January 2000:
Vol. 287. no. 5452, pp. 488 - 491
DOI: 10.1126/science.287.5452.488
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Reports

Transgenic Mouse Model of Stunned Myocardium

Anne M. Murphy, 12* Harald Kögler, 23 Dimitrios Georgakopoulos, 23 Jason L. McDonough, 4 David A. Kass, 23 Jennifer E. Van Eyk, 4 Eduardo Marbán 23

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.

1 Department of Pediatrics,
2 Institute of Molecular Cardiobiology, and
3 Department of Medicine, Johns Hopkins University School of Medicine, Ross Building 1144, 720 Rutland Avenue, Baltimore, MD 21205, USA.
4 Departments of Biochemistry and Physiology, Queen's University, 429 Botterell Hall, Kingston, Ontario, Canada K7L 3W6.
*   To whom correspondence should be addressed. E-mail: murphy{at}jhmi.edu

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