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 for vascular endothelial cells and enhances vascular permeability and edemagenesis. VEGF is also a major regulator of angiogenesis and may be a key target for inhibiting angiogenesis in angiogenesis-associated diseases. Among the extensively studied angiostatic compounds are several corticosteroids when used alone or in combination with heparin. In this study we present evidence for an additional mechanism of action of hydrocortisone, cortisone and dexamethasone in inhibiting edemagenesis or angiogenesis. In cultures of aortic human vascular smooth muscle cells these corticosteroids (1 x 10(-8) to 1 x 10(-12) M) abolished the platelet-derived growth factor-induced (PDGF) expression of the VEGF gene in a dose-dependent manner. In contrast, two precursors of corticosteroids, desoxycorticosterone or pregnenolone, did not affect PDGF-induced VEGF expression. Our findings indicate that the capacity of corticosteroids to reduce edema or to prevent new blood vessel formation may be attributed, at least in part to the ability of these agents to abolish the expression of VEGF.
Nauck
M
M
Department of Clinical Chemistry, University Hospital, Freiburg, Germany.
Karakiulakis
G
G
Perruchoud
A P
AP
Papakonstantinou
E
E
Roth
M
M
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003348:Cortisone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008222:Lymphokines / Q000032:analysis* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000893:Anti-Inflammatory Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003907:Dexamethasone; D003348:Cortisone; D006854:Hydrocortisone