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PMID: 16630019 Published · ppublish English Journal Article Review

Fibrosis in heart disease: understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia.

Immunology ·Vol. 118 ·No. 1 ·2006-05-00 ·Pages 10-24

Khan R, Sheppard R

Abstract

The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor-beta1 (TGF-beta1), a potent stimulator of collagen-producing cardiac fibroblasts. Previously, TGF-beta1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF-beta1. In fact, the pathogenic effects of TGF-beta1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF-beta1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF-beta1 not only in the post-ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF-beta1 is an appropriate target for therapy in a variety of cardiovascular diseases.

MeSH Terms
Arrhythmias, Cardiac/physiopathology Cardiomyopathies/physiopathology Fibrosis Heart Diseases/physiopathology,therapy Heart Valve Diseases/physiopathology Humans Matrix Metalloproteinases/metabolism Myocardium/pathology Transforming Growth Factor beta/antagonists & inhibitors,physiology Transforming Growth Factor beta1
Chemicals
TGFB1 protein, human Transforming Growth Factor beta Transforming Growth Factor beta1 Matrix Metalloproteinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Khan Razi
McGill University, Faculty of Medicine, Montreal, Quebec, Canada. razi.khan@mail.mcgill.ca
Sheppard Richard
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Article Info
Journal
Immunology
Abbr.
Immunology
ISSN
0019-2805
DOI
10.1111/j.1365-2567.2006.02336.x
Email
razi.khan@mail.mcgill.ca
Published
2006-05-00
Pages
10-24
Language
English
Region
England
NLM ID
0374672
PMCID
PMC1782267
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1365-2567.2006.02336.x PMC Full Text View journal details
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