Journal ArticleDOI
Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.
Yow Keat Tham,Yow Keat Tham,Bianca C. Bernardo,Jenny Y. Y. Ooi,Kate L. Weeks,Julie R. McMullen,Julie R. McMullen +6 more
TLDR
New therapeutic approaches either entering clinical trials or in preclinical development, and the challenges that remain in translating these discoveries to new and approved therapies for heart failure are addressed.Abstract:
The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.read more
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Journal ArticleDOI
Mechanisms of physiological and pathological cardiac hypertrophy
TL;DR: The characteristics and underlying mechanisms of physiological and pathological hypertrophy are summarized, and possible therapeutic strategies targeting these pathways to prevent or reverse pathological hyperTrophy are discussed.
Journal 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
TL;DR: 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.
Journal ArticleDOI
Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.
Steven J. Forrester,George W. Booz,Curt D. Sigmund,Thomas M. Coffman,Tatsuo Kawai,Victor Rizzo,Rosario Scalia,Satoru Eguchi +7 more
TL;DR: It is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.
Journal ArticleDOI
Molecular mechanism of doxorubicin-induced cardiomyopathy - An update.
TL;DR: The idea of this review is to bring up to date the recent findings of the mechanism of doxorubicin cardiomyopathies such as calcium dysregulation, endoplasmic reticulum stress, impairment of progenitor cells, activation of immune, ubiquitous system and some other parameters.
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