Alterations in Janus Kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) Signaling in Patients With End-Stage Dilated Cardiomyopathy
- 18 February 2003
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation
- Vol. 107 (6) , 798-802
- https://doi.org/10.1161/01.cir.0000057545.82749.ff
Abstract
Background— Experimental studies indicate that interleukin-6 (IL-6)–related cytokines, signaling via the shared receptor gp130, Janus kinases (JAKs), and signal transducers and activators of transcription (STATs), provide a critical cardiomyocyte survival pathway in vivo. Little is known about the activation of this signaling pathway in the myocardia of patients with end-stage dilated cardiomyopathy (DCM). Methods and Results— We performed a comprehensive expression and activation analysis of IL-6–related cytokines, receptors, signal transducers, and signal transduction inhibitors in left ventricular (LV) myocardia from patients with DCM (n=10) and non-failing (NF) donor hearts (n=5). Differential expression (DCM versus NF) was observed by immunoblotting at each level of the signaling cascade, including receptor ligands (IL-6: −59%, P P P P P P P P P P Conclusion— Signaling via gp130 and JAK-STAT is profoundly altered in DCM. Importantly, tyrosine-phosphorylation of JAK2 is reduced in the face of increased gp130 phosphorylation, indicating impaired downstream activation of this critical pathway in DCM.Keywords
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