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(Circulation Research. 2006;98:985.)
© 2006 American Heart Association, Inc.

Editorials

Partnering Up for Cardiac Hypertrophy

John P. Konhilas, Leslie A. Leinwand

From the Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder.

Correspondence to Leslie A. Leinwand, PhD, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Campus Box 347, Boulder, CO 80309-0347. E-mail leinwand@stripe.colorado.edu

See related article, pages 1089–1097

Key Words: hypertrophy • transcription factors • GATA4 • SRF • myocardin

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

The heart must adapt its mechanical activity to the prevailing hemodynamic demands. When an increased demand is brought about by sustained stimuli such as growth and development, pressure overload, or mutations in sarcomeric proteins, the heart will typically undergo an increase in size caused by myocyte hypertrophy. Underlying this hypertrophic response is the coordinated interaction of distinct signaling modules capable of transmitting and executing modifications in gene expression that lead to alterations in myocyte physiology and long-term cardiac adaptation.¹

One of the more intriguing characteristics of the hypertrophic response is that despite the ability of a wide variety of both pathologic and physiologic stimuli to induce cardiac hypertrophy, distinct cytoplasmic signaling cascades that initiate changes in gene expression converge on a common set of nuclear factors. These factors will then transactivate or repress cardiac genes through cis-regulatory elements. One of these transcription factors, myocardin, that appears to be capable of relaying hypertrophic signals to the genome is the subject of the studies performed by Xing et al² detailed below.

An important hypertrophic transcriptional regulator is the zinc finger–containing transcription factor, GATA4. GATA4 is widely expressed and has been identified as a pivotal regulator of developmental and stress-induced changes in cardiac gene expression.^3,4 GATA4 has been shown to activate numerous genes in the heart by divergent signaling molecules including protein kinase C, calcineurin, and members of the mitogen-activated protein kinase signaling axis.¹ Although GATA4-null embryos arrest before birth,⁵ a point mutation in GATA4 results in septation and coronary vasculature defects,⁶ whereas . . . [Full Text of this Article]