Circulating miR-3656 induces human umbilical vein endothelial cell injury by targeting eNOS and ADAMTS13: a novel biomarker for hypertension
Circulating miR-3656 induces human umbilical vein endothelial cell injury by targeting eNOS and ADAMTS13: a novel biomarker for hypertension
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DOI：
10.1097/hjh.0000000000003010
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发表时间：
2021-09
影响因子：
4.9
通讯作者：
Jikang Shi;Yaxuan Ren;Sainan Liu;Qian Zhao;Fei Kong;Yanbo Guo;Jiayi Xu;Siyu Liu;Y. Qiao-Y
中科院分区：
文献类型：
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作者：
Jikang Shi;Yaxuan Ren;Sainan Liu;Qian Zhao;Fei Kong;Yanbo Guo;Jiayi Xu;Siyu Liu;Y. Qiao-Y
文本中提供补充数字内容背景：高血压作为最常见的慢性病之一，是一个重大的公共卫生问题。既往研究表明，高血压患者存在差异表达的miRNAs。此外，高血压与内皮功能障碍密切相关，miRNA已被确定为内皮功能的重要分子介质。因此，有必要鉴定与高血压相关的特异性miRNAs，并探讨其在高血压发生发展中的分子机制。方法：我们研究了miR-3656循环水平与高血压的相关性。此外，本研究还对miR-3656进行了体外研究，以探讨其治疗高血压的可能机制，采用双荧光素酶报告基因分析法确定了miR-3656的直接靶基因;此外，使用MTS试剂盒、伤口愈合试验、FITC Annexin V凋亡检测试剂盒和管形成试验研究miR-3656对HUVECs增殖、迁移、凋亡和微血管稀疏的影响，相应地。结果：高血压患者循环miR-3656上调。MiR-3656抑制HUVECs的增殖、迁移和血管生成，但促进HUVECs的凋亡。eNOS和ADAMTS 13是miR-3656的直接靶基因，过表达eNOS和ADAMTS 13可阻断miR-3656对HUVECs的作用。结论：miR-3656是一种潜在的高血压生物标志物。miR-3656通过靶向eNOS和ADAMTS 13参与高血压中涉及的内皮细胞损伤。
Supplemental Digital Content is available in the text Background: Hypertension, as one of the most common chronic diseases, is a major public health issue. Previous studies have shown that there are miRNAs differentially expressed in hypertensive patients. In addition, hypertension is closely related to endothelial dysfunction, and miRNAs have been identified as important molecular mediators for endothelial function. Therefore, it is necessary to identify specific miRNAs related to hypertension and explore their molecular mechanism in the progression of hypertension. Methods: We investigated the association of circulating levels of miR-3656 with hypertension. Furthermore, in-vitro studies were performed to investigate its possible mechanisms for hypertension in that the direct target genes of miR-3656 were confirmed using dual-luciferase reporter assay; moreover, the effects of miR-3656 on proliferation, migration, apoptosis, and microvascular rarefaction of HUVECs were investigated using MTS kit, wound-healing assay, FITC Annexin V apoptosis detection kit, and tube formation assay, correspondingly. Results: Circulating miR-3656 was upregulated in patients with hypertension. MiR-3656 suppressed the proliferation, migration, and angiogenesis of HUVECs, but promoted the apoptosis of HUVECs. In addition, eNOS and ADAMTS13 were direct target genes of miR-3656, and overexpression of eNOS and ADAMTS13 abolished the effect of miR-3656 on HUVECs. Conclusion: MiR-3656 is a potential biomarker for hypertension. MiR-3656 is involved in endothelial cellular injury implicated in hypertension by targeting eNOS and ADAMTS13.