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(Circulation Research. 2009;104:e19.)
© 2009 American Heart Association, Inc.

Letters to the Editor

Calcium, Calpains, and Cardiac Hypertrophy: A New Link

Felix M. Heidrich

Department of Pharmacology, Yale University, New Haven, Conn, and, Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany, E-mail felix.heidrich@aya.yale.edu

Barbara E. Ehrlich

Department of Pharmacology, Yale University, New Haven, Conn

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To The Editor:

In the March 28, 2008 issue of Circulation Research, Letavernier et al assessed the effects of calpain inhibition on angiotensin (Ang) II–induced cardiovascular remodeling.¹ These authors used transgenic mice expressing high levels of calpastatin to inhibit Ang II–dependent calpain activation. They show that prevention of Ang II–induced calpain activation is associated with impaired nuclear factor (NF)-B activation in heart tissue, which eventually leads to decreased Ang II–induced cardiac hypertrophy. This finding adds substantial novel information to our understanding of how calpains might be involved in the complex regulation of cardiac hypertrophy. However, compelling evidence as to how calpains are activated by Ang II in the myocardium and how the calpain/calpastatin system is linked to NF-B activation is not provided. In the May 23, 2008 issue of Circulation Research, we show that Ang II induces calcium release via the inositol 1,4,5-trisphosphate receptor (InsP₃R) pathway in cardiomyocytes and that impaired InsP₃R-dependent calcium release after chromogranin B (CGB) knockdown attenuates NF-B activation and leads to decreased production of brain natriuretic peptide (BNP).² Here, we discuss the convergent results of these 2 studies and show that calpain/calpastatin and CGB may be important for developing new strategies in the prevention and treatment of cardiovascular disease.

The calpain/calpastatin system in the heart, and particularly its potential role in the complex regulation of cardiac hypertrophy, is only poorly understood. Calpains are calcium-activated cysteine proteases present in the cytosol as inactive proenzymes. Two isoforms (µ- and m-calpain) are . . . [Full Text of this Article]