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(Circulation Research. 2001;89:3.)
© 2001 American Heart Association, Inc.

Editorial

On Genetics of Dilated Cardiomyopathy and Transgenic Models

All Is Not Crystal Clear in Myopathic Hearts

A. J. Marian

From Baylor College of Medicine, Department of Medicine, Section of Cardiology, Houston, Tex.

Correspondence to A.J. Marian, MD, Associate Professor of Medicine, Section of Cardiology, One Baylor Plaza, 543E, Houston, TX 77030. E-mail amarian@bcm.tmc.edu

Key Words: genetics • dilated cardiomyopathy • transgenic animal models • heat-shock proteins

The B-crystallin protein, the predominant structural protein of the ocular lens, is a member of the small heat shock proteins that is also expressed abundantly in the heart and skeletal muscle.¹ The B-crystallin was initially discovered in the vertebrate ocular lens and was dubbed crystallin because of its role in maintenance of lens transparency.² It is also essential for maintenance of microtubular integrity in striated muscles.³ In the heart, as in the ocular lens, B-crystallin forms soluble multimeres that function as chaperone molecules, facilitating protein folding and translocation.⁴ Thus, the principal function of B-crystallin protein is to prevent unfolding of cellular proteins damaged by all forms of stress. Ischemia and oxidative stress increase the expression of B-crystallin in the heart.⁵ In response to stress, intracellular kinases phosphorylate B-crystallin,⁶ leading to its translocation from the cytosolic pool to Z lines and intercalated disks. Translocated B-crystallin binds to the components of the intermediary filaments and cytoskeletal proteins, such as actin and desmin, and prevents their aggregation.^{3 7} The protective role of B-crystallin in the maintenance of cytoskeletal integrity has been confirmed in gene transfer studies in cultured cardiac myocytes⁸ and in transgenic mice.⁹ Overexpression of B-crystallin protects cardiac myocytes against apoptosis and reperfusion injury.^{8 9}

Interest in B-crystallin has been heightened because of recent elucidation of the genetic basis of desmin-related myopathy (DRM), a familial muscular disorder characterized by skeletal myopathy, heart failure, conduction defect, and arrhythmias. Pathologically, DRM is characterized by the presence of protein aggregates containing desmin in the cytoplasm of striated . . . [Full Text of this Article]

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