Growth factors and endothelial dysfunction

Endothelial dysfunction has been implicated in the pathogenesis of many car diovascular diseases; experimental and clinical studies have shown that end othelial dysfunction may be a key factor in various processes, including ab normal arterial vasomotion, thrombosis or neointimal proliferation. Endothe lial dysfunction has been shown to be a characteristic feature of atheroscl erotic vessels, sites subject to mechanical injury or collateral vessels th at develop in response to severe ischaemia. Fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF ) are important growth factors for endothelial cells in vitro. While VEGF i s specific for endothelial cells, FGFs are also potent growth factors for o ther cell types such as smooth muscle cells. Recent studies have demonstrated the feasibility of using endothelial cell growth factors in vivo. Basic FGF (bFGF) and VEGF have been shown to increa se the development of collateral vessels in ischaemic models and to enhance the extent of endothelial regrowth following arterial injury. The marked a natomical improvement associated with the administration of endothelial cel l growth factors has promoted questions concerning a possible role for thes e factors in endothelial dysfunction. In vivo administration of endothelial cell growth factors is associated wit h significant improvement in endothelium-dependent responses. This effect i s observed with bFGF and VEGF in various animal models of endothelial dysfu nction such as the collateral circulation, the regenerated endothelium foll owing arterial injury and experimental atherosclerosis. While the precise m echanisms underlying this ubiquitous beneficial effect of endothelial cell growth factors are still to be determined, these results do support the con cept of using such factors as a new therapeutic strategy in patients with v ascular diseases.