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(Circulation. 2002;106:1430.)
© 2002 American Heart Association, Inc.

Cardiotrophin-1 in Heart Failure

Michael R. Bristow, MD, PhD; Carlin S. Long, MD

University of Colorado Health Sciences Center, Denver.

Correspondence to Michael R. Bristow, MD, PhD, Division of Cardiology, University of Colorado, Health Sciences Center, 4200 East Ninth Ave, Campus Box B-139, Room BRB 123, Denver, CO 80262.

Key Words: Editorials • heart failure • hypertrophy • signal transduction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Cardiotrophin-1 (CT-1) is a 201 amino acid¹ member of the interleukin (IL)-6 cytokine superfamily, which includes leukemia inhibitory factor (LIF), ciliary neurotrophic factor, IL-11, and oncostatin M.² Cardiotrophin-1 was discovered by Pennica et al² via expression cloning of mouse embryoid bodies, using a cardiac myocyte hypertrophy screen to identify positive clones. CT-1 has hypertrophic and cardioprotective properties and acts through LIF receptor ß/glycoprotein 130 (gp130)-coupled signaling pathways. The LIF receptor binds CT-1, and then gp130 associates with the ligand-receptor complex and transduces the proximal signal. CT-1 intracellular signaling pathways include extracellular signal regulated kinases (ERK), mitogen activated protein (MAP) kinases, the janus kinase (JAK)/signal transducers and activators of transcription (STAT) system, and PI3-kinase/Akt. Downstream mediators of CT-1’s cellular effects include multiple ERK-coupled transcription factors, STAT-3, nuclear factor-B, and heat shock proteins 56, 70, and 90. Cardiac CT-1 expression is increased by hypoxia, where it protects cardiac myocytes from ischemic and reperfusion injury and apoptosis.

See p 1442

As described shortly after its discovery, CT-1 promotes cardiac myocyte hypertrophy by directing sarcomere assembly in series.³ At the ventricular structural level, in-series sarcomeric assembly leads to "eccentric" hypertrophy and chamber dilatation. Thus, increased myocardial expression of CT-1 immediately became a candidate for the molecular basis of pathological hypertrophy and remodeling in dilated cardiomyopathy phenotypes. The cardiac myocyte protective effects were also appreciated early in the investigation of CT-1’s biological properties.⁴ Mice with genetic ablation of gp130 have hypoplastic hearts,⁵ which suggests a role for CT-1 or other IL-6–type cytokines in normal . . . [Full Text of this Article]

Related Article:

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

Oliver Zolk, Leong L. Ng, Russell J. O’Brien, Michael Weyand, and Thomas Eschenhagen
Circulation 2002 106: 1442-1446. [Abstract] [Full Text]

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