Ophthalmology Hospital, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, China.
Biochem Biophys Res Commun. 2013 May 10;434(3):492-7. doi: 10.1016/j.bbrc.2013.03.101. Epub 2013 Apr 10.
Heme oxygenase-1 (HO-1) plays an important role in the vasculature and in the angiogenesis of tumors, wounds and other environments. Retinal pigment epithelial (RPE) cells and choroidal endothelial cells (CECs) are the main cells involved in choroidal neovascularization (CNV), a process in which hypoxia plays an important role. Our aim was to evaluate the role of human RPE-cell HO-1 in the angiogenic activities of cocultured endothelial cells under hypoxia. Small interfering RNA (siRNA) for HO-1 was transfected into human RPE cell line ARPE-19, and zinc protoporphyrin (ZnPP) was used to inhibit HO-1 activity. Knockdown of HO-1 expression and inhibition of HO-1 activity resulted in potent reduction of the expression of vascular endothelial growth factor (VEGF) under hypoxia. Furthermore, knockdown of HO-1 suppressed the proliferation, migration and tube formation of cocultured endothelial cells. These findings indicated that HO-1 might have an angiogenic effect in CNV through modulation of VEGF expression and might be a potential target for treating CNV.
血红素加氧酶-1（HO-1）在血管系统和肿瘤、创伤和其他环境中的血管生成中发挥着重要作用。视网膜色素上皮（RPE）细胞和脉络膜内皮细胞（CEC）是参与脉络膜新生血管（CNV）的主要细胞，缺氧在其中发挥着重要作用。我们的目的是评估人 RPE 细胞 HO-1 在缺氧条件下共培养内皮细胞的血管生成活性中的作用。小干扰 RNA（siRNA）转染入人 RPE 细胞系 ARPE-19，并用锌原卟啉（ZnPP）抑制 HO-1 活性。HO-1 表达的下调和 HO-1 活性的抑制导致缺氧下血管内皮生长因子（VEGF）的表达明显减少。此外，HO-1 的下调抑制了共培养内皮细胞的增殖、迁移和管形成。这些发现表明，HO-1 可能通过调节 VEGF 表达在 CNV 中具有血管生成作用，并且可能是治疗 CNV 的潜在靶点。
