CORTICOSTEROIDS INHIBIT THE EXPRESSION OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS

The vascular endothelial growth factor (VEGF) is a specific mitogen fo r vascular endothelial cells and enhances vascular permeability and ed emagenesis. VEGF is also a major regulator of angiogenesis and may be a key target for inhibiting angiogenesis in angiogenesis-associated di seases. Among the extensively studied angiostatic compounds are severa l corticosteroids when used alone or in combination with heparin. In t his study we present evidence for an additional mechanism of action of hydrocortisone, cortisone and dexamethasone in inhibiting edemagenesi s or angiogenesis. In cultures of aortic human vascular smooth muscle cells these corticosteroids (1x10(-8) to 1x10(-12) M) abolished the pl atelet-derived growth factor-induced (PDGF) expression of the VEGF gen e in a dose-dependent manner. In contrast, two precursors of corticost eroids, desoxycorticosterone or pregnenolone, did not affect PDGF-indu ced VEGF expression. Our findings indicate that the capacity of cortic osteroids to reduce edema or to prevent new blood vessel formation may be attributed, at least in part to the ability of these agents to abo lish the expression of VEGF. (C) 1998 Elsevier Science B.V.