Gao Yanfang, Yin Yuzhu, Xing Xiumei, Zhao Zhiqiang, Lu Yao, Sun Yi, Zhuang Zhixiong, Wang Min, Ji Weidong, He Yun
Guangzhou Key Laboratory of Environmental Pollution and Risk Assessment, Sun Yat-sen University, School of Public Health, Guangzhou, Guangdong 510080, China.
The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Toxicol Lett. 2016 Jul 8;254:22-31. doi: 10.1016/j.toxlet.2016.04.023. Epub 2016 Apr 27.
Human exposure to drinking water contaminated with arsenic is a serious global health concern and it predisposes people to cardiovascular diseases, such as hypertension, atherosclerosis, and microvascular diseases. Although accumulating evidence supports a role for angiogenesis responses to arsenic in the pathogenesis of the cardiovascular disease, the detailed molecular mechanism is not well understood. We aimed to determine the role and mechanism of microRNA (miRNA) in arsenic-induced angiogenesis. In our present study, sodium arsenite (NaAsO2) inhibited angiogenesis by decreasing cells proliferation, migration and tube formation in HUVECs. After NaAsO2 treatment, we found the expression of microRNA-425-5p (miR-425-5p) was reduced in vitro and in vivo and over-expression of miR-425-5p reversed the NaAsO2-induced anti-angiogenesis through its direct target cerebral cavernous malformation 3 (CCM3). Furthermore, we showed that NaAsO2 up-regulated CCM3 expression in vitro and in vivo. In addition, we demonstrated that inhibition of Notch and activation of VEGF/p38 signaling were involved in miR-425-5p blocking NaAsO2-induced anti-angiogenesis.
人类接触受砷污染的饮用水是一个严重的全球健康问题,它使人们易患心血管疾病,如高血压、动脉粥样硬化和微血管疾病。尽管越来越多的证据支持血管生成反应在砷致心血管疾病发病机制中的作用,但详细的分子机制尚未完全了解。我们旨在确定微小RNA(miRNA)在砷诱导的血管生成中的作用和机制。在我们目前的研究中,亚砷酸钠(NaAsO₂)通过降低人脐静脉内皮细胞(HUVECs)的细胞增殖、迁移和管腔形成来抑制血管生成。NaAsO₂处理后,我们发现微小RNA-425-5p(miR-425-5p)在体外和体内的表达均降低,并且miR-425-5p的过表达通过其直接靶点脑海绵状血管畸形3(CCM3)逆转了NaAsO₂诱导的抗血管生成作用。此外,我们表明NaAsO₂在体外和体内上调了CCM3的表达。另外,我们证明Notch的抑制和VEGF/p38信号通路的激活参与了miR-425-5p阻断NaAsO₂诱导的抗血管生成作用。