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 primary effector, angiotensin II (Ang II), in etiology of myocardial hypertrophy and ischemia is well documented. In several animal models, the RAS is activated in cardiac cell types that express the receptor AT1, and/or AT2, 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 maintenance of the local RAS in cardiac hypertrophy and ischemia. Recent studies in our laboratory document that the promoter of the prohormone angiotensinogen (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. STAT5A and STAT6, are selectively activated when the heart is subjected to ischemic injury, whereas activation of STAT3 and STAT5A is involved in myocardial hypertrophy. Blockage of RAS activation by treatment with specific inhibitor promotes a remarkable recovery in functional hemodynamics of the myocardium. Thus, activation of selective sets of STAT proteins constitutes the primary signaling event in the pathogenesis of myocardial hypertrophy and ischemia.
Mascareno
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E
Center for Cardiovascular and Muscle Research, Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn 11203, USA.
Siddiqui
M A
MA
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006331:Heart Diseases / Q000503:physiopathology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D015534:Trans-Activators; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases