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(Circulation. 2000;101:2672.)
© 2000 American Heart Association, Inc.

Editorial

Cytoskeletal Abnormalities in the Failing Heart

Out on a LIM?

Arnold M. Katz, MD

From the Cardiology Division, Department of Medicine, University of Connecticut, Farmington.

Correspondence to Arnold M. Katz, MD, 1592 New Boston Road, PO Box 1048, Norwich, VT 05055-1048. E-mail arnold.m.katz@dartmouth.edu

Key Words: Editorials • heart failure • signal transduction • remodeling • cytoskeleton • cardiomyopathy • cell adhesion molecules

The "modern" era in our understanding of heart failure began around 1990, when unexpected results from clinical trials indicated that maladaptive growth, rather than depressed contractility, is the major cause of the poor prognosis in patients with this syndrome,¹ and that the long-term benefits of angiotensin-converting enzyme inhibitors are due to inhibition of proliferative signaling rather than vasodilation.² The potential importance of molecular abnormalities in the failing heart was further highlighted in 1990 by the discovery that myosin heavy-chain mutations cause hypertrophic cardiomyopathy.³ Many additional sarcomeric protein abnormalities are now known to cause hypertrophic cardiomyopathy,^{4 5} and between a quarter and a third of idiopathic dilated cardiomyopathies appear to be associated with familial disease.^{6 7 8} In contrast to hypertrophic cardiomyopathy, most of the abnormal proteins thus far linked to dilated cardiomyopathy are cytoskeletal, rather than sarcomeric.^{9 10}

The cytoskeleton, like the beams and girders in a modern building, maintains a highly organized structure within cells. Cytoskeletal proteins imbedded in the plasma membrane connect this intracellular matrix with extracellular connective tissue proteins and adjacent cells. In addition to these mechanical functions, the cytoskeleton plays a major role in communication. Cytoskeletal proteins, therefore, do more than maintain cell architecture; their participation in cell signaling is analogous to using the steel framework of a building as the phone system.

The most important signaling function of the cytoskeleton is to modify proliferative responses, such as growth, differentiation, and cell cycling, when cells adhere to the extracellular matrix or when they contact other cells.^{11 12 13 14} Signals generated by cell . . . [Full Text of this Article]

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