Information de reference pour ce titreAccession Number: | 00003017-200302180-00006.
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Author: | Podewski, Edith K. MD; Hilfiker-Kleiner, Denise PhD; Hilfiker, Andres PhD; Morawietz, Henning PhD; Lichtenberg, Artur MD; Wollert, Kai C. MD; Drexler, Helmut MD
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Institution: | From the Departments of Cardiology and Angiology (E.K.P., D.H.K., A.H., K.C.W., H.D.), and Cardiovascular Surgery (A.L.), Hannover Medical School, Hannover, Germany, and the Institute of Pathophysiology (H.M.), University of Halle-Wittenberg, Germany.
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Title: | |
Source: | Circulation. 107(6):798-802, February 18, 2003.
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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 <0.01; leukemia inhibitory factor [LIF]: +54%, P <0.05), receptor subunits (LIF receptor: -16%, P <0.05), signaling molecules (the Janus kinase TYK2: -48%, P <0.01; STAT3: -47%, P <0.01), and suppressors of cytokine signaling (SOCS1: +97%, P <0.05; SOCS3: -49%, P <0.01). Tyrosine-phosphorylation status of gp130 was increased (+60%, P <0.05), whereas tyrosine-phosphorylation status of JAK2 was reduced in DCM (-72%, P <0.01). Moreover, as shown by immunohistochemistry, the number of STAT3-positive cardiomyocytes was reduced in DCM (-42%, P <0.01).
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.
(C) 2003 American Heart Association, Inc.
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Author Keywords: | cardiomyopathy; interleukins; signal transduction.
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Language: | English.
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Document Type: | Brief Rapid Communications.
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Journal Subset: | Clinical Medicine.
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ISSN: | 0009-7322
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NLM Journal Code: | daw, 0147763
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