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(Circulation Research. 2009;104:829.)
© 2009 American Heart Association, Inc.

Editorials

Gelsolin and Cardiac Myocyte Apoptosis

A New Target in the Treatment of Postinfarction Remodeling

Ryosuke Nishio, Akira Matsumori

From the Division of Emergency Medicine (R.N.), Kyoto University Hospital; and Department of Cardiovascular Medicine (A.M.), Kyoto University Graduate School of Medicine, Japan.

Correspondence to Akira Matsumori, MD, PhD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail amat@kuhp.kyoto-u.ac.jp

See related article, pages 896–904

Key Words: gelsolin • apoptosis • cardiac remodeling • myocardial infarction

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

	Introduction

 
Cardiac remodeling is among the most important problems in patients with heart failure.^1,2 Ventricular remodeling involves numerous processes, involving molecular alterations, myocardial changes, and the abnormal geometry of the chamber. As a consequence of myocardial infarction (MI), ventricular remodeling occurs immediately as an adaptive response to maintain cardiac output.³ However, ventricular function and prognosis deteriorate with ongoing remodeling. MI triggers an inflammatory response, including cytokine activation, a cascade of intracellular signaling, and neurohormonal activation^4,5 These processes result in scar formation and myocyte loss through necrosis, apoptosis, and autophagy.⁶ An MI has been shown to be a prominent inducer of cardiomyocyte apoptosis, which, in turn, may contribute to progressive postinfarction remodeling, as demonstrated by recently reported animal and human studies.⁷ Yet, the pathophysiological mechanisms of apoptosis in cardiac myocytes remain unclear. The elucidation of the mechanisms of cardiomyocyte apoptosis may lead to an improved understanding of postinfarction remodeling and thereby possibly improve patient care.

Cardiomyocytic apoptosis post-MI is induced by angiotensin II and β1-adrenergic stimulation, reactive oxygen species, overstretch, and nitric oxide.⁸ Apoptotic programmed cell death is characterized by DNA fragmentation attributable to the activation of an endogenous endonuclease. This endonuclease-mediated breakdown of DNA in apoptosis is activated through "caspase-dependent" pathways or "caspase-independent" pathways (Figure).⁹

View larger version (36K):   Figure. Gelsolin and cell death pathways in cardiac myocytes. Gelsolin can translocate to the nucleus and elevate DNase I through the gelsolin/HIF-1/DNase I pathway, in part, in a caspase-independent manner. Caspase-3 can cleave gelsolin between residues Asp352 and Gly353. The N-terminal gelsolin fragment . . . [Full Text of this Article]

Related Article:

Gelsolin Regulates Cardiac Remodeling After Myocardial Infarction Through DNase I–Mediated Apoptosis

Guo Hua Li, Yu Shi, Yu Chen, Mei Sun, Sawsan Sader, Yuichiro Maekawa, Sara Arab, Fayez Dawood, Manyin Chen, Geoffrey De Couto, Youan Liu, Masahiro Fukuoka, Stanley Yang, Ming Da Shi, Lorrie A. Kirshenbaum, Christopher A. McCulloch, and Peter Liu
Circ. Res. 2009 104: 896-904. [Abstract] [Full Text] [PDF]