This Article Full Text Full Text (PDF) All Versions of this Article: 106/12/1442    most recent 01.CIR.0000033117.39335.DFv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zolk, O. Articles by Eschenhagen, T. Search for Related Content PubMed PubMed Citation Articles by Zolk, O. Articles by Eschenhagen, T. Related Collections Congestive Growth factors/cytokines Related Article

(Circulation. 2002;106:1442.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Augmented Expression of Cardiotrophin-1 in Failing Human Hearts Is Accompanied by Diminished Glycoprotein 130 Receptor Protein Abundance

Oliver Zolk, MD; Leong L. Ng, MD; Russell J. O’Brien, MB; Michael Weyand, MD; Thomas Eschenhagen, MD

From the Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany (O.Z., T.E.); the Department of Medicine and Therapeutics, University of Leicester, Leicester, United Kingdom (L.L.N., R.J.O.); and Zentrum für Herzchirurgie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany (M.W.).

Correspondence to Dr Oliver Zolk, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstr. 17, 91054 Erlangen, Germany. E-mail Zolk{at}pharmakologie.uni-erlangen.de

Background— Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily, is a potent inducer of cardiomyocyte hypertrophy that prolongs myocyte survival. Although cardiac CT-1 gene expression is known to be upregulated in some animal models of congestive heart failure, the activation state of the CT-1 system in patients with congestive heart failure is unknown.

Methods and Results— This study was designed to determine left ventricular expression of CT-1 and its glycoprotein 130 (gp130)/leukemia inhibitory factor receptor complex in human end-stage heart failure due to ischemic and dilated cardiomyopathy. In addition, we investigated the activation state of signal transducer and activator of transcription 3 (STAT3), the downstream effector of gp130 signaling. In the failing left ventricular myocardium, expression levels of CT-1 mRNA and protein were significantly increased by 142% and 68%, respectively, compared with non-failing donor hearts. Immunohistochemistry confirmed the increased expression of CT-1 in cardiac myocytes. Although gp130 gene expression was increased by 91% (P<0.001), gp130 protein abundance was significantly diminished by 34% in the failing myocardium. In contrast, leukemia inhibitory factor receptor and suppressor of cytokine signaling-3 protein concentrations were not changed. In addition, the ratio of activated tyrosine phosphorylated STAT3 to total STAT3 was not significantly altered in failing hearts compared with non-failing controls.

Conclusions— Our data suggest that gp130 receptor downregulation balances enhanced CT-1 expression in human heart failure and thereby inhibits excessive activation of the gp130 signaling pathway.

Key Words: genes • heart failure • growth substances • receptors • signal transduction

Related Article:

Cardiotrophin-1 in Heart Failure

Michael R. Bristow and Carlin S. Long
Circulation 2002 106: 1430-1432. [Full Text]

This article has been cited by other articles:

				B. Lopez, J. M. Castellano, A. Gonzalez, J. Barba, and J. Diez Association of Increased Plasma Cardiotrophin-1 With Inappropriate Left Ventricular Mass in Essential Hypertension Hypertension, November 1, 2007; 50(5): 977 - 983. [Abstract] [Full Text] [PDF]

				D. W. Ho, Z. F. Yang, C. K. Lau, K. H. Tam, J. Y. To, R. T. Poon, and S. T. Fan Therapeutic Potential of Cardiotrophin 1 in Fulminant Hepatic Failure: Dual Roles in Antiapoptosis and Cell Repair Arch Surg, November 1, 2006; 141(11): 1077 - 1084. [Abstract] [Full Text] [PDF]

				C. J. Pemberton, S. D. Raudsepp, T. G. Yandle, V. A. Cameron, and A. M. Richards Plasma cardiotrophin-1 is elevated in human hypertension and stimulated by ventricular stretch Cardiovasc Res, October 1, 2005; 68(1): 109 - 117. [Abstract] [Full Text] [PDF]

				O. Zolk, S. Engmann, F. Munzel, and R. Krajcik Chronic cardiotrophin-1 stimulation impairs contractile function in reconstituted heart tissue Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1214 - E1221. [Abstract] [Full Text] [PDF]

				J. G. Coles, C. Boscarino, M. Takahashi, D. Grant, A. Chang, J. Ritter, X. Dai, C. Du, G. Musso, H. Yamabi, et al. Cardioprotective stress response in the human fetal heart J. Thorac. Cardiovasc. Surg., May 1, 2005; 129(5): 1128 - 1136. [Abstract] [Full Text] [PDF]

				D. H. Freed, R. H. Cunnington, A. L. Dangerfield, J. S. Sutton, and I. M.C. Dixon Emerging evidence for the role of cardiotrophin-1 in cardiac repair in the infarcted heart Cardiovasc Res, March 1, 2005; 65(4): 782 - 792. [Abstract] [Full Text] [PDF]

				X. Zheng, D. Zhou, C. Y. Seow, and T. R Bai Cardiotrophin-1 alters airway smooth muscle structure and mechanical properties in airway explants Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1165 - L1171. [Abstract] [Full Text] [PDF]

				O. Zolk, F. Munzel, and T. Eschenhagen Effects of chronic endothelin-1 stimulation on cardiac myocyte contractile function Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1248 - H1257. [Abstract] [Full Text] [PDF]

				A. Gonzalez, M. A Fortuno, R. Querejeta, S. Ravassa, B. Lopez, N. Lopez, and J. Diez Cardiomyocyte apoptosis in hypertensive cardiomyopathy Cardiovasc Res, September 1, 2003; 59(3): 549 - 562. [Abstract] [Full Text] [PDF]

				Y. Nakaoka, K. Nishida, Y. Fujio, M. Izumi, K. Terai, Y. Oshima, S. Sugiyama, S. Matsuda, S. Koyasu, K. Yamauchi-Takihara, et al. Activation of gp130 Transduces Hypertrophic Signal Through Interaction of Scaffolding/Docking Protein Gab1 With Tyrosine Phosphatase SHP2 in Cardiomyocytes Circ. Res., August 8, 2003; 93(3): 221 - 229. [Abstract] [Full Text] [PDF]

				C. Ancey, E. Menet, P. Corbi, S. Fredj, M. Garcia, C. Rucker-Martin, J. Bescond, F. Morel, J. Wijdenes, J.-C. Lecron, et al. Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation Cardiovasc Res, July 1, 2003; 59(1): 78 - 85. [Abstract] [Full Text] [PDF]

				M. A. Fortuno, A. Gonzalez, S. Ravassa, B. Lopez, and J. Diez Clinical implications of apoptosis in hypertensive heart disease Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1495 - H1506. [Full Text] [PDF]

				E. K. Podewski, D. Hilfiker-Kleiner, A. Hilfiker, H. Morawietz, A. Lichtenberg, K. C. Wollert, and H. Drexler Alterations in Janus Kinase (JAK)-Signal Transducers and Activators of Transcription (STAT) Signaling in Patients With End-Stage Dilated Cardiomyopathy Circulation, February 18, 2003; 107(6): 798 - 802. [Abstract] [Full Text] [PDF]

				M. R. Bristow and C. S. Long Cardiotrophin-1 in Heart Failure Circulation, September 17, 2002; 106(12): 1430 - 1432. [Full Text] [PDF]