Stat proteins as intracellular regulators of resistance to myocardial injury in the context of cardiac remodeling and targeting for therapy.

Abstract

The roles of STAT (signal transducers and activators of transcription) proteins are widely discussed in relation to other agents like IFN-γ that are involved in cardiovascular diseases. STAT3 protects cardiomyocytes during endotoxic shock and ischemia and prolongs survival of these cells by activation of antiapoptotic genes like Bcl-2 and c-Fos. Moreover, IL-6 dependent expression of STAT3 is probably responsible for hypertrophy of cardiomyocytes. On the contrary, STAT1 mediates cell death by induction of caspase-1. STAT6 probably enhances cellular damage in myocardial infraction, which is significantly reduced in mice with the knockout STAT6 gene. Considering these facts, we attempted to review in this paper the role of STAT proteins in myocardial remodeling, highlighting STAT3 as a potent mediator of cardioprotection. Our review also aims to acquaint a broad audience of internal medicine practitioners with the STAT3-related molecular mechanisms that underlie the therapeutic properties of such widely administered drugs as angiotensin II type 1 (AT1) receptor antagonists and HMG-CoA reductase inhibitors, such as losartan and lovastatin.