This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Williams, R. S. Search for Related Content PubMed PubMed Citation Articles by Williams, R. S. Related Collections Other myocardial biology Remodeling Cell signalling/signal transduction Gene regulation Heart failure - basic studies Myocardial cardiomyopathy disease

(Circulation. 2002;105:2242.)
© 2002 American Heart Association, Inc.

Calcineurin Signaling in Human Cardiac Hypertrophy

R. Sanders Williams, MD

From Duke University School of Medicine, Durham, NC.

Correspondence to R. Sanders Williams, MD, Duke University School of Medicine, Davidson Building, Green Zone, Room 125, Box 2927, Durham, NC 27710. E-mail willi397@mc.duke.edu

Key Words: Editorials • hypertrophy • calcium • genes • heart failure

On the basis of studies in cell and animal models, a great diversity of signaling molecules have been implicated in stimulus–response pathways by which hypertrophic growth of the myocardium is controlled. It remains unclear, however, which signal transduction pathways are pertinent to the common forms of cardiac hypertrophy that lead to heart failure and sudden death in humans.

See p 2265

The initial observation in 1998¹ that calcineurin, a calmodulin-dependent protein phosphatase, is capable of driving cardiac hypertrophy, heart failure, and death in experimental animal models received special attention for several reasons. Previous evidence suggested that dysregulation of calcium metabolism is an integral feature of stresses that promote hypertrophy, and calcineurin was known to be abundant in cardiomyocytes, reinforcing the plausibility of its proposed role as a key mediator of hypertrophic signaling. Perhaps most intriguing is the fact that calcineurin is the target of drugs already approved for use in humans to inhibit T-cell activation and prevent rejection of transplanted organs, validating the concept that nodal points in complex signaling networks exist and can indeed serve as targets for clinically efficacious drugs. Initial studies indicated that calcineurin-inhibitory drugs could prevent or repress pathological forms of cardiac hypertrophy induced by a variety of stimuli.²

Over the past 3 years, enthusiasm for calcineurin as a potential target for drugs to prevent heart failure in humans has waxed and waned^3–7 as many laboratories have focused attention on this pathway with sometimes discrepant results.^8–15 The administration of calcineurin-inhibitory drugs has proven ineffective or counterproductive . . . [Full Text of this Article]

This article has been cited by other articles:

				A. Pedram, M. Razandi, M. Aitkenhead, and E. R. Levin Estrogen Inhibits Cardiomyocyte Hypertrophy in Vitro: ANTAGONISM OF CALCINEURIN-RELATED HYPERTROPHY THROUGH INDUCTION OF MCIP1 J. Biol. Chem., July 15, 2005; 280(28): 26339 - 26348. [Abstract] [Full Text] [PDF]

				R. S. Williams and B. H. Annex Plasticity of Myocytes and Capillaries: A Possible Coordinating Role for VEGF Circ. Res., July 9, 2004; 95(1): 7 - 8. [Full Text] [PDF]

				R.S. WILLIAMS and P. ROSENBERG Calcium-dependent Gene Regulation in Myocyte Hypertrophy and Remodeling Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 339 - 344. [Abstract] [PDF]