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.
Booz
George W
GW
The Cardiovascular Research Institute, Division of Molecular Cardiology, The Texas A&M University System Health Science Center, College of Medicine, Temple, Texas 76504, USA. gbooz@medicine.tamu.edu
Day
Jonathan N E
JN
Baker
Kenneth M
KM
D000808:Angiotensinogen / Q000096:biosynthesis; D017209:Apoptosis / Q000502:physiology; D019898:Autocrine Communication; D006332:Cardiomegaly / Q000503:physiopathology; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D020935:MAP Kinase Signaling System / Q000502:physiology; D008894:Milk Proteins; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins; D012084:Renin-Angiotensin System / Q000502:physiology*; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D015534:Trans-Activators; D000808:Angiotensinogen; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human