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Molecular regulation of cardiac hypertrophy

Molecular regulation of cardiac hypertrophy
Molecular regulation of cardiac hypertrophy
Heart failure is one of the leading causes of mortality in the western world and encompasses a wide spectrum of cardiac pathologies. When the heart experiences extended periods of elevated workload, it undergoes hypertrophic enlargement in response to the increased demand. Cardiovascular disease, such as that caused by myocardial infarction, obesity or drug abuse promotes cardiac myocyte hypertrophy and subsequent heart failure. A number of signalling modulators in the vasculature milieu are known to regulate heart mass including those that influence gene expression, apoptosis, cytokine release and growth factor signalling. Recent evidence using genetic and cellular models of cardiac hypertrophy suggests that pathological hypertrophy can be prevented or reversed and has promoted an enormous drive in drug discovery research aiming to identify novel and specific regulators of hypertrophy. In this review we describe the molecular characteristics of cardiac hypertrophy such as the aberrant re-expression of the fetal gene program. We discuss the various molecular pathways responsible for the co-ordinated control of the hypertrophic program including: natriuretic peptides, the adrenergic system, adhesion and cytoskeletal proteins, IL-6 cytokine family, MEK-ERK1/2 signalling, histone acetylation, calcium-mediated modulation and the exciting recent discovery of the role of microRNAs in controlling cardiac hypertrophy. Characterisation of the signalling pathways leading to cardiac hypertrophy has led to a wealth of knowledge about this condition both physiological and pathological. The challenge will be translating this knowledge into potential pharmacological therapies for the treatment of cardiac pathologies.
cardiac, hypertrophy, molecular, signalling, transcription
1357-2725
2023-2039
Barry, Sean P.
ea289198-c2f3-4d24-9c15-93b2c439632a
Davidson, Sean M.
b8eeed87-5d86-42ca-8844-25bf6887253c
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Barry, Sean P.
ea289198-c2f3-4d24-9c15-93b2c439632a
Davidson, Sean M.
b8eeed87-5d86-42ca-8844-25bf6887253c
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db

Barry, Sean P., Davidson, Sean M. and Townsend, Paul A. (2008) Molecular regulation of cardiac hypertrophy. International Journal of Biochemistry & Cell Biology, 40 (10), 2023-2039. (doi:10.1016/j.biocel.2008.02.020).

Record type: Article

Abstract

Heart failure is one of the leading causes of mortality in the western world and encompasses a wide spectrum of cardiac pathologies. When the heart experiences extended periods of elevated workload, it undergoes hypertrophic enlargement in response to the increased demand. Cardiovascular disease, such as that caused by myocardial infarction, obesity or drug abuse promotes cardiac myocyte hypertrophy and subsequent heart failure. A number of signalling modulators in the vasculature milieu are known to regulate heart mass including those that influence gene expression, apoptosis, cytokine release and growth factor signalling. Recent evidence using genetic and cellular models of cardiac hypertrophy suggests that pathological hypertrophy can be prevented or reversed and has promoted an enormous drive in drug discovery research aiming to identify novel and specific regulators of hypertrophy. In this review we describe the molecular characteristics of cardiac hypertrophy such as the aberrant re-expression of the fetal gene program. We discuss the various molecular pathways responsible for the co-ordinated control of the hypertrophic program including: natriuretic peptides, the adrenergic system, adhesion and cytoskeletal proteins, IL-6 cytokine family, MEK-ERK1/2 signalling, histone acetylation, calcium-mediated modulation and the exciting recent discovery of the role of microRNAs in controlling cardiac hypertrophy. Characterisation of the signalling pathways leading to cardiac hypertrophy has led to a wealth of knowledge about this condition both physiological and pathological. The challenge will be translating this knowledge into potential pharmacological therapies for the treatment of cardiac pathologies.

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More information

Published date: 2008
Keywords: cardiac, hypertrophy, molecular, signalling, transcription

Identifiers

Local EPrints ID: 59491
URI: https://eprints.soton.ac.uk/id/eprint/59491
ISSN: 1357-2725
PURE UUID: b466a458-39a0-4cc6-80fd-38494deefea9

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Date deposited: 08 Sep 2008
Last modified: 13 Mar 2019 20:30

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Contributors

Author: Sean P. Barry
Author: Sean M. Davidson
Author: Paul A. Townsend

University divisions

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