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(Circulation Research. 2002;90:1240.)
© 2002 American Heart Association, Inc.

Editorials

Importance of Integrin Signaling in Myocyte Growth and Survival

Dhandapani Kuppuswamy

From the Cardiology Division of the Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, and the Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC.

Correspondence to Dhandapani Kuppuswamy, PhD, Gazes Cardiac Research Institute, 114 Doughty St, Charleston, SC 29425-2221. E-mail kuppusd@musc.edu

Key Words: cardiomyocyte • integrins • focal adhesion kinase • hypertrophy • apoptosis

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

Both skeletal and cardiac myocytes undergo developmentally programmed terminal differentiation with subsequent adaptation to increased demands for mechanical output being met by hypertrophy. However, there is a fundamental difference between these two striated muscle types in terms of their ability to respond to muscle injury and cell death: in skeletal muscle, stem cells proliferate and replace lost myocytes; in cardiac muscle, the occurrence of such a mechanism is very low. Therefore, the sole structural response of the heart to cell loss (myocardial infarction) or pathological mechanical overload (hemodynamic pressure or volume overload) is myocyte hypertrophic growth.

Often growth is triggered when specific cell-surface receptors are occupied by their ligands, such as growth factors and hormones, which results in the activation of either intrinsic or associated kinases. In addition to these established pathways, there is growing evidence that signals generated at the focal adhesion sites after integrin engagement with specific extracellular matrix (ECM) proteins significantly contribute to growth and survival (for review, see Schaller¹). Whereas multiple pathways might be necessary for the hypertrophic phenotype of cardiomyocytes, Heidkamp and colleagues² in this issue of Circulation Research demonstrate the importance of myocyte survival signals transmitted by focal adhesion kinase (FAK), a nonreceptor tyrosine kinase that is localized to the cell attachment site (focal adhesions).

Integrins are a family of cell-surface receptors, composed of noncovalently associated and ß subunits. There are at least 20 different integrin subtypes that are formed from 12 different and 8 different ß subunits, and many of these subtypes . . . [Full Text of this Article]

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