Endothelial cell derived growth factors in pulmonary vascular hypertension

In pulmonary hypertension there is remodelling of the pulmonary vessels. This renders the vasculature unresponsive to vasodilators and hence once this remodelling has occurred, patients are difficult to treat. Future therapies will be aimed at preventing or reversing remodelling, but in order to develop these therapies we need a greater knowledge of the remodelling process. Remodelling occurs in all three vascular layers and, in the past, most attention has focused on medial hypertrophy and hyperplasia. This review concentrates on factors that might lead to adventitial hypertrophy, in particular factors affecting adventitial fibroblast function. It is proposed that the endothelial cell orchestrates the activity of the fibroblasts that in turn leads to adventitial thickening. Various factors that might act on the endothelial cell to produce a variety of growth promoting and chemotactic factors are discussed. In particular, our work on the actions of endothelin on pulmonary vascular fibroblasts is described and it is suggested that factors such as hypoxia could cause remodelling by the stimulation of endothelial cell derived factors which would, in turn, stimulate adventitial fibroblast chemotaxis and replication.