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(Circulation Research. 2008;103:1194.)
© 2008 American Heart Association, Inc.

Editorials

A New (Heat) Shocking Player in Cardiac Hypertrophy

Thomas M. Vondriska, Yibin Wang

From the Division of Molecular Medicine, Departments of Anesthesiology, Physiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles.

Correspondence to Yibin Wang, PhD, Division of Molecular Medicine, Departments of Anesthesiology, Physiology and Medicine, David Geffen School of Medicine at UCLA, Room BH 569, CSH, Los Angeles, CA 90095. E-mail yibinwang@mednet.ucla.edu

Key Words: cardiac • hypertrophy • Hsp70 • HDAC2 • gene • regulation

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

Hypertrophic growth of cardiac myocytes is a common result of different physiological and pathological stresses. It remains a subject of considerable debate whether hypertrophy is a compensatory process that becomes maladaptive in diseased hearts or a direct contributor to the pathogenesis of heart failure. Nevertheless, many types of stressors, mechanical or neural/hormonal, induce hypertrophy and this phenotype is an independent risk factor in heart failure. Therefore, much effort has been devoted to uncovering mechanisms of hypertrophic growth, with the expectation that intercepting this process clinically may halt the disease progression of heart failure. It is firmly established that hypertrophic growth involves alterations in gene regulation, excitation–contraction coupling, extracellular matrix remodeling, and energy metabolism.

Among molecules known to regulate hypertrophic gene expression, histone deacetylases (HDACs) have been identified as key players in the pathological setting.^1,2 HDACs function as corepressors by targeted modification of local accessibility of chromatin to transcriptional machinery. HDACs are counteracted by histone acetyl transferases (HATs) to achieve dynamic regulation of gene expression depending on prevailing cellular stress and/or developmental conditions. There are 3 classes (I, II, and IV) of "classic" HDACs, consisting of 11 family members in addition to 7 sirtuin family members. Among the classic HDACs, class II HDAC members (HDAC4, -5, -7, and -9) have all been shown to negatively regulate hypertrophy by repressing MEF/GATA/NFAT-mediated gene expression.³ Interestingly, such negative regulatory activity is acetylase activity independent. In contrast, a recent report⁴ implicated the class I HDAC member HDAC2 as a positive regulator of hypertrophy and showed . . . [Full Text of this Article]