Abstract
Biochemical studies in endothelial cells (ECs) and genetic studies in mice and humans have yielded major insights into the role of transforming growth factor β (TGF-β) and its downstream Smad effectors in embryonic vascular morphogenesis and in the establishment and maintenance of vessel wall integrity. These studies showed that TGF-β signaling is of critical importance for normal vascular development and physiology. They also indicated the involvement of two distinct TGF-β signaling cascades within ECs, namely the activin receptor-like kinase 5 (ALK5)-Smad2/3 pathway and the ALK1-Smad1/5 pathway. Aberrant TGF-β signaling forms the basis for several vascular disorders such as hereditary hemorrhagic telengiectasia and primary pulmonary hypertension as well as neovascularization during tumorigenesis. This review describes the role of TGF-β in angiogenesis and some of the controversial issues concerning TGF-β signaling through ALK1 and ALK5 in ECs.
| Original language | English |
|---|---|
| Pages (from-to) | 301-307 |
| Number of pages | 7 |
| Journal | Trends in Cardiovascular Medicine |
| Volume | 13 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Oct 2003 |
Bibliographical note
Funding Information:The authors thank Drs. Peter ten Dijke and Jon Halstead for invaluable discussions and critical reading of the manuscript. They also acknowledge grant support from the Dutch Organization for Scientific Research (MW 902-16-295), the European Union (QLG1-CT-2001-01032), and the Netherlands Heart Foundation (grant 99-046).