Interplay between the cardiac renin angiotensin system and JAK-STAT signaling: role in cardiac hypertrophy, ischemia/reperfusion dysfunction, and heart failure.

Recent studies have shown that the JAK-STAT signaling pathway plays a central role in cardiac pathophysiology. JAK-STAT signaling has been implicated in pressure overload-induced cardiac hypertrophy and remodeling, ischemic preconditioning, and ischemia/reperfusion-induced cardiac dysfunction. The different STAT family members expressed in cardiac myocytes appear to be linked to different, and at times, opposite responses, such as cell growth/survival and apoptosis. Thus, differential activation and/or selective inhibition of the STAT proteins by agonists for G-protein coupled receptors, such as angiotensin II, may contribute to cardiac dysfunction during ischemia and heart failure. In addition, JAK-STAT signaling may represent one limb of an autocrine loop for angiotensin II generation, that serves to amplify the actions of angiotensin II on cardiac muscle. The purpose of this article is to provide an overview of recent findings that have been made for JAK-STAT signaling in cardiac myocytes and to highlight some unresolved issues for future investigation. The central focus of this review is on recent studies suggesting that modulation or activation of JAK-STAT signaling by ANG II has pathological consequences for heart function.