| First Author | Merkle S | Year | 2007 |
| Journal | Circ Res | Volume | 100 |
| Issue | 5 | Pages | 645-53 |
| PubMed ID | 17303764 | Mgi Jnum | J:133697 |
| Mgi Id | MGI:3783950 | Doi | 10.1161/01.RES.0000260203.55077.61 |
| Citation | Merkle S, et al. (2007) A role for caspase-1 in heart failure. Circ Res 100(5):645-53 |
| abstractText | 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. |
