Copyright © 2007, European Society of Cardiology
TGF-β signaling in vascular fibrosis
Vascular and Renal Research Laboratory, Fundación Jiménez Diaz, Universidad Autónoma Madrid, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
* Corresponding author. Tel.: +34 1 5504800x3168; fax: +34 1 5494764. Email address: mruizo{at}fjd.es
Transforming growth factor-β (TGF-β) participates in the pathogenesis of multiple cardiovascular diseases, including hypertension, restenosis, atherosclerosis, cardiac hypertrophy and heart failure. TGF-β exerts pleiotropic effects on cardiovascular cells, regulating cell growth, fibrosis and inflammation. TGF-β has long been believed to be the most important extracellular matrix regulator. We review the complex mechanisms involved in TGF-β-mediated vascular fibrosis that includes the Smad signaling pathway, activation of protein kinases and crosstalk between these pathways. TGF-β blockade diminishes fibrosis in experimental models, however better antifibrotic targets are needed for an effective therapy in human fibrotic diseases. A good candidate is connective tissue growth factor (CTGF), a downstream mediator of TGF-β-induced fibrosis. Among the different factors involved in vascular fibrosis, Angiotensin II (AngII) has special interest. AngII can activate the Smad pathway independent of TGF-β and shares with TGF-β many intracellular signals implicated in fibrosis. Blockers of AngII have demonstrated beneficial effects on many cardiovascular diseases and are now one of the best options to block TGF-β fibrotic responses. A better knowledge of the intracellular signals of TGF-β can provide novel therapeutic approaches for fibrotic diseases.
KEYWORDS Angiotensin; Fibrosis; Smooth muscle; MAPK kinases; Signal transduction
Time for primary review 26 days
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