This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gottlieb, R. Search for Related Content PubMed PubMed Citation Articles by Gottlieb, R. Related Collections Related Article

(Circulation Research. 2005;96:1036.)
© 2005 American Heart Association, Inc.

Editorials

ICE-ing the Heart

Roberta Gottlieb

From the Scripps Research Institute, La Jolla, Calif.

Correspondence to Dr Roberta A. Gottlieb, Department of Molecular and Experimental Medicine, The Scripps Research Institute MEM220, 10550 North Torrey Pines Road, La Jolla, CA. Email robbieg@scripps.edu

See related article, pages 1103–1109

Key Words: caspase-1 • apoptosis • myocardial ischemia • endotoxin • transgenic

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

In this issue of Circulation Research, Syed et al¹ report that overexpression of caspase-1 (ICE) contributes to myocardial ischemia/reperfusion injury. Transgenic mice were generated using the alpha-myosin heavy chair promoter to drive caspase-1 expression in the heart. The mice expressed caspase-1 30-fold more than the nontransgenics. Despite this massive overexpression, no spontaneous caspase activation or apoptosis was noted, and there was no apparent cardiac phenotype. However, endotoxin exposure and ischemia/reperfusion were associated with increased caspase-1 and -3 activation in the transgenic mice, suggesting that caspase-1 contributes to myocardial pathology in these settings. Cell culture studies were used to bolster the notion that caspase-1 activated caspase-3 directly rather than through upstream caspases.

Missing from this study was any analysis of cytokine processing, although the primary role of caspase-1 is to process interleukin-1-beta (IL-1ß) and IL-18, and potentially IL-1, IL-6, and tumor necrosis factor alpha- (TNF-). Enhanced caspase-1 activity and IL-18 have been reported after myocardial infarction, suggesting a role for caspase-1 in postischemic inflammation and injury.² Frantz et al who showed that targeted deletion of caspase-1 was associated with reduced postoperative mortality and less left ventricular dilatation after myocardial infarction.³ The authors also noted reduced IL-18 levels and decreased matrix metalloproteinase-3 (MMP-3) in the caspase-1-null animals after myocardial infarction, suggesting that cytokine signaling contributed to the injury process.

Caspase-1 can be processed to the active form by caspase-11,⁴ which is activated in response to ischemia or endotoxin exposure. Caspase-11 is also capable of activating caspase-3 directly,⁵ although its . . . [Full Text of this Article]

Related Article:

Proapoptotic Effects of Caspase-1/Interleukin-Converting Enzyme Dominate in Myocardial Ischemia

Faisal M. Syed, Harvey S. Hahn, Amy Odley, Yiru Guo, Jesus G. Vallejo, Roy A. Lynch, Douglas L. Mann, Roberto Bolli, and Gerald W. Dorn, II
Circ. Res. 2005 96: 1103-1109. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				A. Abbate, F. N. Salloum, E. Vecile, A. Das, N. N. Hoke, S. Straino, G. G.L. Biondi-Zoccai, J.-E. Houser, I. Z. Qureshi, E. D. Ownby, et al. Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, Inhibits Apoptosis in Experimental Acute Myocardial Infarction Circulation, May 20, 2008; 117(20): 2670 - 2683. [Abstract] [Full Text] [PDF]

				E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [Abstract] [Full Text] [PDF]