Alprostadil suppresses angiogenesis in vitro and in vivo in the murine Matrigel plug assay
Alprostadil suppresses angiogenesis in vitro and in vivo in the murine Matrigel plug assay
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DOI：
10.1038/sj.bjp.0705051
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发表时间：
2003-01-01
影响因子：
7.3
通讯作者：
Vicentini, LM
中科院分区：
文献类型：
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作者：
Cattaneo, MG;Pola, S;Vicentini, LM
1前列腺素E-1（PGE（1），alcohydil）作为血管扩张剂用于治疗外周血管疾病。2以前的报道表明PGE（1）具有促血管生成作用。3我们研究了PGE（1）与α-环糊精复合物对血管生成过程的体外和体内作用。与预期相反，我们发现，在人脐静脉内皮细胞（HUVECs）中，PGE（1）抑制Matrigel中的增殖、迁移和毛细血管样结构的形成。4通过RT-PCR研究，在HUVECs中检测到PG受体的EP 2和EP 3亚型的表达。5 PGE（1）单独在微摩尔浓度下刺激腺苷酸环化酶活性，而在纳摩尔浓度下，增强了毛喉素诱导的cAMP积累。6 8-溴腺苷-3 '：5 '-环一磷酸盐（Br-cAMP）模拟PGE（1）对内皮细胞生长、运动性和管形成的抑制作用。7 Sulprostone（一种PG受体EP 3亚型激动剂）模拟PGE（1）的体外抗血管生成作用，而butaprost（一种EP 2受体激动剂）则无此作用。8最后，在小鼠血管生成的栓塞试验模型中，PGE（1）对Matrigel新生血管形成显示出强烈的抑制作用。9因此，PGE（1）在体外和体内具有强烈的抗血管生成活性。
1 Prostaglandin E-1 (PGE(1), alprostadil) is used as a vasodilator for the treatment of peripheral vascular diseases.2 Previous reports suggested a pro-angiogenic effect for PGE(1).3 We studied the in vitro and in vivo effect of PGE(1), complexed with alpha-cyclodextrin, on the angiogenic process. Contrary to what was expected, we found that, in human umbilical vein endothelial cells (HUVECs), PGE(1) inhibited proliferation, migration and capillary-like structure formation in Matrigel.4 By RT-PCR studies, the expression of the EP2 and EP3 subtypes of the PG receptor was detected in HUVECs.5 PGE(1) alone stimulated adenylate cyclase activity at micromolar concentrations, while at nanomolar concentrations potentiated the forskolin-induced cAMP accumulation.6 8-Bromoadenosine-3':5'-cyclic monophosphate (Br-cAMP) mimicked the inhibitory effect of PGE(1) on endothelial cell growth, motility and tube formation.7 Sulprostone, an agonist at the EP3 subtype of PG receptors, mimicked the in vitro anti-angiogenic effects of PGE(1), while butaprost, an EP2 receptor agonist, had no effect.8 Finally, in the plug assay model of angiogenesis in mice, PGE(1) showed a strong inhibitory effect on Matrigel neovascularization.9 Thus, PGE(1) possesses strong anti-angiogenic activity in vitro and in vivo.