The role of Jak/STAT signaling in heart tissue renin-angiotensin system

The involvement of the Renin Angiotensin System (RAS) and the role of its p rimary effector, angiotensin II (Ang II), in etiology of myocardial hypertr ophy and ischemia is well documented. In several animal models, the RAS is activated in cardiac cell types that express the receptor AT(1), and/or AT( 2), through which the Ang II mediated effects are promoted. In this article , we briefly review recent experimental evidence on the critical role of a prominent signaling pathway, the Jak/Stat pathway in activation and mainten ance of the local RAS in cardiac hypertrophy and ischemia. Recent studies i n our laboratory document that the promoter of the prohormone angiotensinog en (Ang) gene serves as the target site for STAT proteins, thereby linking the Jak/Stat pathway to activation of heart tissue autocrine Ang II loop. S tat5A and Stat6, are selectively activated when the heart is subjected to i schemic injury, whereas activation of Stat3 and Stat5A is involved in myoca rdial hypertrophy. Blockage of RAS activation by treatment with specific in hibitor promotes a remarkable recovery in functional hemodynamics of the my ocardium. Thus, activation of selective sets of Stat proteins constitutes t he primary signaling event in the pathogenesis of myocardial hypertrophy an d ischemia.