Extracellular control of TGFβ signalling in vascular development and disease

The intracellular mechanism of transforming growth factor-beta (TGF beta) 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 TGF beta. It seems that elastic extracellular matrix (ECM) components have a crucial role in controlling TGF beta signalling, while soluble and membrane bound forms of TGF beta co-receptors add further layers of regulation. Together, these extracellular interactions determine the final bioavailability of TGF beta to vascular cells, and dysregulation is associated with an increasing number of vascular pathologies.