Transforming Growth Factor (TGF)-β signaling in cardiac remodeling

By M. Dobaczewski, Wei Chen, Nikolaos G. Frangogiannis. Journal of Molecular and Cellular Cardiology, 2010

923 citations recorded by the source corpus.

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.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/0bdf0995c45540dcecfaafc521f7395cb85ca238

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

In Molecular Biology

In Surgery

Citations in the corpus

The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. (2016, background): “cells and the time course of its upregulation after MI, TGFβ1 may serve as the master switch regulating the transition from inflammation to fibrosis.(199) Neutralization experiments”
The Pathogenesis of Cardiac Fibrosis (2013, positive): “Perhaps the best-characterized fibrogenic growth factor [221], TGF-β is markedly and consistently activated in experimental models of cardiac fibrosis [222] and in fibrotic human hearts [223, 224].”
Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice (2016, background): “…plays an important role in the pathogenesis of cardiac remodeling through its effects on cardiomyocytes, immune cells, and mesenchymal cells (Dobaczewski et al., 2011), and 13 of the module-5 genes are directly involved in TGF-b signaling, with four genes, including Pcocle (Moali et al.,…”
TGF-β signaling in fibrosis (2011, background): “Because the Smad3 pathway appears to play an essential role in TGF-bmediated fibrosis, Smad3 inhibition through the administration of endogenous inhibitors (such as Smad7), or through the use of small molecule inhibitors (such as halofuginone) may hold promise.”
Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration (2016, background): “TGF-β is probably the best-characterized pro-fibrotic growth factor (Dobaczewski et al. 2011; Kong et al. 2014).”
Fibroblast-specific TGF-β-Smad2/3 signaling underlies cardiac fibrosis. (2017, positive): “TGF-β is considered a “master” cytokine/growth factor produced within injured or diseased tissues, where it activates fibroblasts and facilitates ECM production (15, 16).”