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Transforming growth factor (TGF)-β signaling in cardiac remodeling

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Dobaczewski, Marcin, Chen, Wei, Frangogiannis, Nikolaos G.·2011·Journal of Molecular and Cellular Cardiology
DOI 10.1016/j.yjmcc.2010.10.033
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Abstract

Myocardial TGF-β expression is upregulated in experimental models of myocardial infarction and cardiac hypertrophy, and in patients with dilated or hypertrophic cardiomyopathy. Through its effects on cardiomyocytes, mesenchymal and immune cells, TGF-β plays an important role in the pathogenesis of cardiac remodeling and fibrosis. TGF-β overexpression in the mouse heart is associated with fibrosis and hypertrophy. Endogenous TGF-β plays an important role in the pathogenesis of cardiac fibrotic and hypertrophic remodeling, and modulates matrix metabolism in the pressure-overloaded heart. In the infarcted heart, TGF-β deactivates inflammatory macrophages, while promoting myofibroblast transdifferentiation and matrix synthesis through Smad3-dependent pathways. Thus, TGF-β may serve as the “master switch” for the transition of the infarct from the inflammatory phase to formation of the scar. Because of its crucial role in cardiac remodeling, the TGF-β system may be a promising therapeutic target for patients with heart failure. However, efforts to translate these concepts into therapeutic strategies, in order to prevent cardiac hypertrophy and fibrosis, are hampered by the complex, pleiotropic and diverse effects of TGF-β signaling, by concerns regarding deleterious actions of TGF-β inhibition and by the possibility of limited benefit in patients receiving optimal treatment with ACE inhibitors and β-adrenergic blockers. Dissection of the pathways responsible for specific TGF-β-mediated actions and understanding of cell-specific actions of TGF-β are needed to design optimal therapeutic strategies.

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Metadata

Authors
Dobaczewski, M., Chen, W., & Frangogiannis, N. G.
Venue
Journal of Molecular and Cellular Cardiology
Publisher
Elsevier BV
Published
2011-10
Volume
51
Issue
4
Pages
600-606
ISSN
0022-2828 (ISSN-L)
DOI
10.1016/j.yjmcc.2010.10.033
OpenAlex
W2059104750
Cited by
934
References
5
FWCI
13.90
Type
journal article
Language
en
Open access
green
Licence
  • www.elsevier.com/tdm/userlicense/1.0/ (tdm)
  • www.elsevier.com/legal/tdmrep-license (tdm)
Funders
National Institutes of Health (R01 HL76246, R01 HL85440)

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Dobaczewski, M., Chen, W., & Frangogiannis, N. G. (2011). Transforming growth factor (TGF)-β signaling in cardiac remodeling. Journal of Molecular and Cellular Cardiology. https://doi.org/10.1016/j.yjmcc.2010.10.033

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