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(Circulation. 1998;97:1433-1435.)
© 1998 American Heart Association, Inc.

Editorials

Success in Failure

Modeling Cardiac Decompensation in Transgenic Mice

W. Robb MacLellan, MD; ; Michael D. Schneider, MD

From the Molecular Cardiology Unit (W.R.M., M.D.S.), Departments of Medicine (W.R.M., M.D.S.), Cell Biology (M.D.S.), and Molecular Physiology and Biophysics (M.D.S.), and Houston Veterans Affairs Medical Center (W.R.M.), Baylor College of Medicine, Houston, Tex.

Correspondence to Michael D. Schneider, MD, Molecular Cardiology Unit, Baylor College of Medicine, One Baylor Plaza, Room 506C, Houston, TX 77030. E-mail michaels@bcm.tmc.edu

Key Words: Editorials • hypertrophy • pressure

The temporal link between cardiac hypertrophy and progressive myocardial failure has been recognized for some time, although mechanistic connections have been elusive. More than 100 years ago, Sir William Osler described three classic stages of cardiac hypertrophy, which culminate in "broken compensation."¹ Much research in recent years has focused on identifying specific hypertrophic stimuli and dissecting the corresponding signaling pathways to elucidate the events responsible for this maladaptive transition. The development and widespread adoption of molecular techniques to modify the genome, chiefly in small mammals, have fueled this search and have provided investigators a means to test the physiological consequences of single gene defects, engineered in vivo. Toward this end, both gain- and loss-of-function mutations have been used in efforts to understand the biochemical pathways and molecular mechanisms underlying the transition from cardiac hypertrophy to failure, at least in mice, culminating in a robust and still-growing array of transgenic models with a cardiomyopathic phenotype similar in many respects to the human disease state.

In this issue of Circulation, Sakata et al² report the progressive decompensation of cardiac function after experimental pressure overload in transgenic mice that overexpress the GTP-binding protein, G_q, selectively in cardiac muscle. G_q-coupled receptors mediate signaling by -adrenergic agonists, angiotensin II, and endothelin, among other molecules with trophic or functional effects on the myocardium. Previous studies amply demonstrate the ability of G_q-coupled receptors and G_q itself to stimulate hypertrophy in neonatal cardiac myocytes grown in cell culture³ ; however, their respective role in . . . [Full Text of this Article]

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