Nauck M, Karakiulakis G, Perruchoud A P, Papakonstantinou E, Roth M
Department of Clinical Chemistry, University Hospital, Freiburg, Germany.
Eur J Pharmacol. 1998 Jan 12;341(2-3):309-15. doi: 10.1016/s0014-2999(97)01464-7.
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.
血管内皮生长因子（VEGF）是血管内皮细胞的一种特异性促有丝分裂原，可增强血管通透性并引发水肿。VEGF也是血管生成的主要调节因子，可能是血管生成相关疾病中抑制血管生成的关键靶点。在广泛研究的血管生成抑制化合物中，有几种皮质类固醇单独使用或与肝素联合使用时具有此作用。在本研究中，我们提供了氢化可的松、可的松和地塞米松在抑制水肿形成或血管生成方面的另一种作用机制的证据。在人主动脉血管平滑肌细胞培养物中，这些皮质类固醇（1×10⁻⁸至1×10⁻¹²M）以剂量依赖的方式消除了血小板衍生生长因子诱导的（PDGF）VEGF基因表达。相比之下，皮质类固醇的两种前体，脱氧皮质酮或孕烯醇酮，不影响PDGF诱导的VEGF表达。我们的研究结果表明，皮质类固醇减轻水肿或防止新血管形成的能力，至少部分可归因于这些药物消除VEGF表达的能力。
