Open AccessJournal Article
IS103 Loss of a gp130 Cardiac Muscle Cell Survival Pathway Is a Critical Event in the Onset of Heart Failure During Biomechanical Stress
Hisao Hirota,Kenneth R. Chien +1 more
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TLDR
Cardiac myocyte apoptosis is a critical point in the transition between compensatory cardiac hypertrophy and heart failure and gp130-dependent cytokines may represent a novel therapeutic strategy for preventing in vivo heart failure.Abstract:
Biomechanical stress is a major stimulus for cardiac hypertrophy and the transition to heart failure. By generating mice that harbor a ventricular restricted knockout of the gp130 cytokine receptor via Cre-IoxP-mediated recombination, we demonstrate a critical role for a gp130-dependent myocyte survival pathway in the transition to heart failure. Such conditional mutant mice have normal cardiac structure and function, but during aortic pressure overload, these mice display rapid onset of dilated cardiomyopathy and massive induction of myocyte apoptosis versus the control mice that exhibit compensatory hypertrophy. Thus, cardiac myocyte apoptosis is a critical point in the transition between compensatory cardiac hypertrophy and heart failure. gp130-dependent cytokines may represent a novel therapeutic strategy for preventing in vivo heart failure.read more
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Cardiac Hypertrophy: The Good, the Bad, and the Ugly
TL;DR: Recent insights into hypertrophic signaling are summarized, several novel antihypertrophic strategies are considered and modulation of myocardial growth without adversely affecting contractile function is increasingly recognized as a potentially auspicious approach in the prevention and treatment of heart failure.
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Cardiac Dysfunction in the Trastuzumab Clinical Trials Experience
Andrew D. Seidman,Clifford A. Hudis,Mary Kathryn Pierri,Steven Shak,Virginia E. Paton,Mark Ashby,Maureen E. Murphy,Stanford J. Stewart,Deborah L. Keefe +8 more
TL;DR: Trastuzumab is associated with an increased risk of cardiac dysfunction, which is greatest in patients receiving concurrent anthracyclines, and in most patients with metastatic breast cancer, the risk of CD can be justified given the improvement in overall survival previously reported with trastuzUMab.
Journal ArticleDOI
Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.
TL;DR: Since the IL-6/gp130/STAT3 signaling pathway is involved in both B cell growth and differentiation into plasma cells it is likely to play a central role in the generation of plasma cell neoplasias.
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Cardiac fibroblast: the renaissance cell.
TL;DR: Insight is provided into the various properties of cardiac fibroblasts that helps illustrate their importance in maintaining proper cardiac function, as well as their critical role in the remodeling heart.
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Signaling Pathways for Cardiac Hypertrophy and Failure
John J. Hunter,Kenneth R. Chien +1 more
TL;DR: This review highlights the ways in which molecular insights are leading to new therapeutic targets in patients with acquired forms of heart failure and Morphologic Classification of Cardiac Hypertrophy.
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Apoptosis in the Failing Human Heart
Giorgio Olivetti,R Abbi,Federico Quaini,Jan Kajstura,Cheng W,James A. Nitahara,Eugenio Quaini,C. Di Loreto,Carlo Alberto Beltrami,Stanislaw Krajewski,John C. Reed,Piero Anversa +11 more
TL;DR: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.
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Gp130 and the interleukin-6 family of cytokines
Tetsuya Taga,Tadamitsu Kishimoto +1 more
TL;DR: This paper reviews recent progress in the study of the interleukin-6 family of cytokines and gp130 and describes how the dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors.
Journal ArticleDOI
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