%0 Journal Article %1 Merkle2007 %A Merkle, S. %A Frantz, S. %A Schon, M. P. %A Bauersachs, J. %A Buitrago, M. %A Frost, R. J. %A Schmitteckert, E. M. %A Lohse, M. J. %A Engelhardt, S. %D 2007 %J Circ Res %K 1/biosynthesis/deficiency/genetics/*physiology 3/physiology 9/physiology Animals Apoptosis/genetics/physiology Cardiac/enzymology/pathology Caspase Cultured Disease Failure/*enzymology/genetics/*pathology Female Heart Humans Knockout Mice Myocytes, Progression Rats Transgenic Up-Regulation/genetics/physiology Cell %N 5 %P 645-53 %T A role for caspase-1 in heart failure %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17303764 %V 100 %X Apoptosis of cardiomyocytes is increased in heart failure and has been implicated in disease progression. The activation of "proapoptotic" caspases represents a key step in cardiomyocyte apoptosis. In contrast, the role of "proinflammatory" caspases (caspases 1, 4, 5, 11, 12) is unclear. Here, we study the cardiac function of caspase-1. Gene array analysis in a murine heart failure model showed upregulation of myocardial caspase-1. In addition, we found increased expression of caspase-1 protein in murine and human heart failure. Mice with cardiomyocyte-specific overexpression of caspase-1 developed heart failure in the absence of detectable formation of interleukin (IL)-1beta or IL-18 and inflammation. Transgenic caspase-1 induced primary cardiomyocyte apoptosis before structural and molecular signs of myocardial remodeling occurred. In contrast, deletion of endogenous caspase-1 was beneficial in the setting of myocardial infarction-induced heart failure. Furthermore, caspase-1-deficient mice were protected from ischemia/reperfusion-induced cardiomyocyte apoptosis. Studies in primary rat cardiomyocytes indicated that caspase-1 induces cardiomyocyte apoptosis primarily through activation of caspases-3 and -9. In contrast to previous findings, which imply a proinflammatory role of caspase-1, these data suggest a primary proapoptotic role for caspase-1 in cardiomyocytes. Our findings support a functional role for caspase-1-mediated myocardial apoptosis contributing to the progression of heart failure.

@article{Merkle2007, abstract = {Apoptosis of cardiomyocytes is increased in heart failure and has been implicated in disease progression. The activation of "proapoptotic" caspases represents a key step in cardiomyocyte apoptosis. In contrast, the role of "proinflammatory" caspases (caspases 1, 4, 5, 11, 12) is unclear. Here, we study the cardiac function of caspase-1. Gene array analysis in a murine heart failure model showed upregulation of myocardial caspase-1. In addition, we found increased expression of caspase-1 protein in murine and human heart failure. Mice with cardiomyocyte-specific overexpression of caspase-1 developed heart failure in the absence of detectable formation of interleukin (IL)-1beta or IL-18 and inflammation. Transgenic caspase-1 induced primary cardiomyocyte apoptosis before structural and molecular signs of myocardial remodeling occurred. In contrast, deletion of endogenous caspase-1 was beneficial in the setting of myocardial infarction-induced heart failure. Furthermore, caspase-1-deficient mice were protected from ischemia/reperfusion-induced cardiomyocyte apoptosis. Studies in primary rat cardiomyocytes indicated that caspase-1 induces cardiomyocyte apoptosis primarily through activation of caspases-3 and -9. In contrast to previous findings, which imply a proinflammatory role of caspase-1, these data suggest a primary proapoptotic role for caspase-1 in cardiomyocytes. Our findings support a functional role for caspase-1-mediated myocardial apoptosis contributing to the progression of heart failure.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Merkle, S. and Frantz, S. and Schon, M. P. and Bauersachs, J. and Buitrago, M. and Frost, R. J. and Schmitteckert, E. M. and Lohse, M. J. and Engelhardt, S.}, biburl = {https://www.bibsonomy.org/bibtex/26adf90f7823e9b65d240822b6c2023b5/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {2e7fa707b18000198559791544e7aab2}, intrahash = {6adf90f7823e9b65d240822b6c2023b5}, issn = {1524-4571 (Electronic) 1524-4571 (Linking)}, journal = {Circ Res}, keywords = {1/biosynthesis/deficiency/genetics/*physiology 3/physiology 9/physiology Animals Apoptosis/genetics/physiology Cardiac/enzymology/pathology Caspase Cultured Disease Failure/*enzymology/genetics/*pathology Female Heart Humans Knockout Mice Myocytes, Progression Rats Transgenic Up-Regulation/genetics/physiology Cell}, month = {Mar 16}, note = {Merkle, Sabine Frantz, Stefan Schon, Michael P Bauersachs, Johann Buitrago, Monika Frost, Robert J A Schmitteckert, Eva M Lohse, Martin J Engelhardt, Stefan Comparative Study Research Support, Non-U.S. Gov't United States Circulation research Circ Res. 2007 Mar 16;100(5):645-53. Epub 2007 Feb 15.}, number = 5, pages = {645-53}, shorttitle = {A role for caspase-1 in heart failure}, timestamp = {2010-12-14T18:21:26.000+0100}, title = {A role for caspase-1 in heart failure}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17303764}, volume = 100, year = 2007 }