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Review

Nature Reviews Molecular Cell Biology 8, 857–869 (1 November 2007) | doi:10.1038/nrm2262

Extracellular control of TGF|[beta]| signalling in vascular development and disease

Peter ten Dijke & Helen M. Arthur

The intracellular mechanism of transforming growth factor-β (TGFβ) signalling via kinase receptors and SMAD effectors is firmly established, but recent studies of human cardiovascular syndromes such as Marfan syndrome and pre-eclampsia have refocused attention on the importance of regulating the availability of active extracellular TGFβ. It seems that elastic extracellular matrix (ECM) components have a crucial role in controlling TGFβ signalling, while soluble and membrane bound forms of TGFβ co-receptors add further layers of regulation. Together, these extracellular interactions determine the final bioavailability of TGFβ to vascular cells, and dysregulation is associated with an increasing number of vascular pathologies.