title: Jak/STAT/SOCS signaling circuits and associated cytokine-mediated inflammation and hypertrophy in the heart.
abstract: Cytokines are important mediators of cardiac disease. Accumulating evidence indicates that members of the interleukin-6 family of cytokines promote cardiac hypertrophy through the activation of the Janus kinase-signal transducer and activator of transcription (Jak/STAT) pathway. Aberrant Jak/STAT signaling may promote progression from hypertrophy to heart failure. Suppressor of cytokine signaling (SOCS) proteins are underexplored, negative regulators of Jak/STAT signaling. SOCS proteins may also interact with other inflammatory pathways known to affect cardiac function. A better understanding of the therapeutic potential of these proteins may lead to the controlled progression of heart failure and the limitation of myocardial depression. This review summarizes the cardiophysiological effect of the IL-6 cytokine family, outlines the mechanistic pathway of Jak/STAT signaling, explores the regulatory role of SOCS proteins in the heart, and discusses the potential of using SOCS proteins clinically.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Terrell
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crisostomo
authors.forename: George M
authors.initials: GM
authors.lastname: Wairiuko
authors.forename: Meijing
authors.initials: M
authors.lastname: Wang
authors.forename: Eric D
authors.initials: ED
authors.lastname: Morrell
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D015850:Interleukin-6 / Q000502:physiology*; D008954:Models, Biological; D050791:STAT Transcription Factors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*
chemical_list: D015850:Interleukin-6; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins