Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui District, Shanghai, 20033, China.
Metab Brain Dis. 2018 Oct;33(5):1679-1688. doi: 10.1007/s11011-018-0276-5. Epub 2018 Jun 24.
Angiogenesis is an important pathophysiological response to cerebral ischemia. PTEN is a lipid phosphatase whose loss activates PI3K/Akt signaling, which is related to HIF-1α upregulation and enhanced angiogenesis in human cancer cells. However, the specific roles of PTEN in endothelial cell functions and angiogenesis after cerebral ischemia remain unknown. Therefore, we sought to examine the potential effects of PTEN inhibition on post-ischemic angiogenesis in human blood vessel cells and to determine the underlying mechanism. In this present study, human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation (OGD), cell proliferation, migration and apoptosis, in vitro tube formation and expression of PTEN/Akt pathway and angiogenic factors were examined in HUVECs after treatment with PTEN inhibitor bisperoxovanadium (bpV) at different doses. The results showed that bpV significantly increased the cell proliferation and reduced cell apoptosis indicating that the drug exerts a cytoprotective effect on HUVECs with OGD exposure. bpV also enhanced cell migration and tube formation in HUVECs following OGD, and upregulated HIF-1α and VEGF expressions, but attenuated endostatin expression. Additionally, western blotting analysis demonstrated that Akt phosphorylation in HUVECs was significantly increased after bpV treatment. These findings suggest that PTEN inhibition promotes post-ischemic angiogenesis in HUVECs after exposure to OGD and this enhancing effect might be achieved through activation of the Akt signal cascade.
血管生成是脑缺血后的一种重要病理生理反应。PTEN 是一种脂质磷酸酶，其缺失会激活 PI3K/Akt 信号通路，与 HIF-1α 的上调和人癌细胞中的血管生成增强有关。然而，PTEN 在脑缺血后内皮细胞功能和血管生成中的具体作用尚不清楚。因此，我们试图研究 PTEN 抑制对人血管细胞缺血后血管生成的潜在影响，并确定其潜在机制。在本研究中，我们将人脐静脉内皮细胞（HUVECs）暴露于氧葡萄糖剥夺（OGD）中，检测不同剂量的 PTEN 抑制剂双过氧钒（bpV）处理后 HUVECs 中的细胞增殖、迁移和凋亡、体外管形成以及 PTEN/Akt 通路和血管生成因子的表达。结果表明，bpV 显著增加了细胞增殖，减少了细胞凋亡，表明该药物对 OGD 暴露的 HUVECs 具有细胞保护作用。bpV 还增强了 HUVECs 在 OGD 后的细胞迁移和管形成，并上调了 HIF-1α 和 VEGF 的表达，但下调了内皮抑素的表达。此外，Western blot 分析表明，bpV 处理后 HUVECs 中的 Akt 磷酸化明显增加。这些发现表明，PTEN 抑制促进了 OGD 暴露后的 HUVEC 缺血后血管生成，这种增强作用可能是通过激活 Akt 信号级联实现的。
