miR-455-5p介导的ADMA代谢和转运网络调控在内皮损伤中的作用

内源性一氧化氮合酶抑制物非对称性二甲基精氨酸（ADMA）通过抑制NO生成，引起内皮功能不全，促进AS的发生发展。我们发现负责ADMA合成、水解、转运的关键酶蛋白精氨酸甲基转移酶1（PRMT1）、二甲基精氨酸二甲胺水解酶1（DDAH1）、阳离子氨基酸转运体2（SLC7A2）均存在miR-455-5p潜在靶点，预实验证实DDAH1是miR-455-5p的靶基因，AS斑块中miR-455-5p表达显著升高，PRMT1、DDAH1、SLC7A2表达显著降低，以上结果提示miR-455-5p可能通过网络调控PRMT1/DDAH1/SLC7A2通路影响ADMA浓度，引起内皮功能障碍参与AS发生发展。本研究首次结合临床研究和细胞实验，探讨miR-455-5p与AS的关系，阐明其机制是否与网络调控PRMT1/DDAH1/SLC7A2通路有关，有助于阐明AS形成的机制，为AS防治提供新的思路。

Asymmetric dimethylarginine (ADMA) is an endogenous NOS inhibitor of which can competitively inhibit NO production, results in endothelial dysfunction and atherosclerosis. We found the enzymes which is responsible for ADMA synthesis(PRMT1)、hydrolyzation(DDAH1)、transport(SLC7A2) were potential target for miR-455-5p.Our expriment also demonstrate that DDAH1 is the target gene of miR-455-5p and miR-455-5p is significate increased, PRMT1、DDAH1、SLC7A2 mRNA are downregulated in atherosclerosis plaque. So we hypothesis that miR-455-5p can affect ADMA concentration by directly network regulate PRMT1/DDAH1/SLC7A2 passway and result in atherosclerosis. This study was first time to evaluate whether miR-455-5p can affect ADMA concentration by PRMT1/DDAH1/SLC7A2 passway. It can be benefit for illuminate the mechanism of atherosclerosis.