Document Detail


Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies.
MedLine Citation:
PMID:  20438756     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Cardiac hypertrophy can be defined as an increase in heart mass. Pathological cardiac hypertrophy (heart growth that occurs in settings of disease, e.g. hypertension) is a key risk factor for heart failure. Pathological hypertrophy is associated with increased interstitial fibrosis, cell death and cardiac dysfunction. In contrast, physiological cardiac hypertrophy (heart growth that occurs in response to chronic exercise training, i.e. the 'athlete's heart') is reversible and is characterized by normal cardiac morphology (i.e. no fibrosis or apoptosis) and normal or enhanced cardiac function. Given that there are clear functional, structural, metabolic and molecular differences between pathological and physiological hypertrophy, a key question in cardiovascular medicine is whether mechanisms responsible for enhancing function of the athlete's heart can be exploited to benefit patients with pathological hypertrophy and heart failure. This review summarizes key experimental findings that have contributed to our understanding of pathological and physiological heart growth. In particular, we focus on signaling pathways that play a causal role in the development of pathological and physiological hypertrophy. We discuss molecular mechanisms associated with features of cardiac hypertrophy, including protein synthesis, sarcomeric organization, fibrosis, cell death and energy metabolism and provide a summary of profiling studies that have examined genes, microRNAs and proteins that are differentially expressed in models of pathological and physiological hypertrophy. How gender and sex hormones affect cardiac hypertrophy is also discussed. Finally, we explore how knowledge of molecular mechanisms underlying pathological and physiological hypertrophy may influence therapeutic strategies for the treatment of cardiovascular disease and heart failure.
Authors:
Bianca C Bernardo; Kate L Weeks; Lynette Pretorius; Julie R McMullen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-12
Journal Detail:
Title:  Pharmacology & therapeutics     Volume:  128     ISSN:  1879-016X     ISO Abbreviation:  Pharmacol. Ther.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905840     Medline TA:  Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  191-227     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Affiliation:
Cardiac Hypertrophy Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
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