Bausero P, Ben-Mahdi M, Mazucatelli J, Bloy C, Perrot-Applanat M
Remodelage Vasculaire, Institut National de la Santé et de la Recherche Médicale U460, Centre Hospitalier Universitaire Xavier Bichât, 75870 Paris Cedex, France.
Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2033-42. doi: 10.1152/ajpheart.2000.279.5.H2033.
Vascular endothelial growth factor (VEGF) promotes neovascularization, microvascular permeability, and endothelial proliferation. We described previously VEGF mRNA and protein induction by estradiol (E2) in human endometrial fibroblasts. We report here E2 induction of VEGF expression in human venous muscle cells [smooth muscle cells (SMC) from human saphenous veins; HSVSMC] expressing both ER-alpha and ER-beta estrogen receptors. E2 at 10(-9) to 10(-8) M increases VEGF mRNA in HSVSMC in a time-dependent manner (3-fold at 24 h), as analyzed by semiquantitative RT-PCR. This level of induction is comparable with E2 endometrial induction of VEGF mRNA. Tamoxifen and hypoxia also increase HSVSMC VEGF mRNA expression over control values. Immunocytochemistry of saphenous veins and isolated SMC confirms translation of VEGF mRNA into protein. Immunoblot analysis of HSVSMC-conditioned medium detects three bands of 18, 23, and 28 kDa, corresponding to VEGF isoforms of 121, 165, and 189 amino acids. Radioreceptor assay of the conditioned medium produced by E2-stimulated HSVSMC reveals an increased VEGF secretion. Our data indicate that VEGF is E2, tamoxifen, and hypoxia inducible in cultured HSVSMC and E2 inducible in aortic SMC, suggesting E2 modulation of VEGF effects in angiogenesis, vascular permeability, and integrity.
血管内皮生长因子（VEGF）可促进新血管形成、微血管通透性及内皮细胞增殖。我们之前曾描述过雌二醇（E2）可在人子宫内膜成纤维细胞中诱导VEGF mRNA和蛋白表达。我们在此报告，E2可在同时表达雌激素受体α和β的人静脉肌细胞（来自人隐静脉的平滑肌细胞；HSVSMC）中诱导VEGF表达。通过半定量RT-PCR分析，10^(-9)至10^(-8)M的E2可使HSVSMC中的VEGF mRNA呈时间依赖性增加（24小时时增加3倍）。这种诱导水平与E2在子宫内膜中诱导VEGF mRNA的水平相当。他莫昔芬和缺氧也可使HSVSMC的VEGF mRNA表达高于对照值。隐静脉和分离的SMC的免疫细胞化学证实了VEGF mRNA可翻译成蛋白质。对HSVSMC条件培养基的免疫印迹分析检测到18、23和28 kDa的三条带，分别对应于121、165和189个氨基酸的VEGF异构体。对E2刺激的HSVSMC产生的条件培养基进行放射受体分析显示VEGF分泌增加。我们的数据表明，VEGF在培养的HSVSMC中可被E2、他莫昔芬和缺氧诱导，在主动脉SMC中可被E2诱导，提示E2在血管生成、血管通透性和完整性方面对VEGF效应具有调节作用。
