TGF-β signaling in vascular fibrosis

M Ruiz-Ortega, J Rodríguez-Vita… - Cardiovascular …, 2007 - academic.oup.com
Cardiovascular research, 2007academic.oup.com
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 …
Abstract
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.
Oxford University Press