doi: 10.1161/01.RES.0000015425.11187.19
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© 2002 American Heart Association, Inc.
Editorials |
IGF-1 Overexpression Rescues the Failing Heart
From The Cardiovascular Institute, Loyola University Chicago Stritch School of Medicine, Maywood, Ill.
Correspondence to Allen M. Samarel, MD, The Cardiovascular Institute, Loyola University Medical Center, 2160 South First Ave, Maywood, IL 60153. E-mail asamare@lumc.edu
Key Words: growth hormone • apoptosis • cardiac regeneration
Congestive heart failure (CHF) is a syndrome affecting nearly 5 million Americans with 550 000 new cases diagnosed annually. Despite recent advances in pharmacological therapy, the enormity of the clinical problem has stimulated cardiovascular scientists to test a variety of new and provocative hypotheses that may ultimately prove useful in CHF prevention and treatment. One such novel approach is addressed by Welch et al1 in this issue of Circulation Research. They tested the hypothesis that insulin-like growth factor-1 (IGF-1), a peptide growth factor involved in cardiomyocyte proliferation, differentiation, and cell survival, can positively affect CHF progression in a transgenic mouse model of dilated cardiomyopathy. The study provides new and important information about the cellular mechanisms leading to ventricular remodeling and also adds to the current controversy regarding the roles of cardiomyocyte apoptosis and regeneration in the pathogenesis of CHF.
What’s Wrong With the TOT Mouse?
Welch et al1 make use of two previously characterized transgenic mouse lines in a selective crossbreeding experiment. Dilated cardiomyopathy was modeled by overexpression of the cytoskeletal protein tropomodulin, to produce homozygous animals (tropomodulin-overexpressing transgenic [TOT] mice) with many of the features of human idiopathic dilated cardiomyopathy.2 Tropomodulin is an actin-binding protein that associates with the pointed ends of actin filaments. This occurs late in the process of myofibrillogenesis and is thought to be responsible for maintaining the final length of thin filaments in mature, striated myofibrils.3 Sussman and coworkers have previously shown that tropomodulin overexpression in cultured cardiomyocytes produced shortened actin filaments and myofibrillar degeneration, whereas antisense downregulation of tropomodulin
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