Li Min, Li Gang, Yang Yanyan, Zong Jinbao, Fu Xiuxiu, Htet Aung Lynn Htet, Li Xiaolu, Li Tianxiang, Wang Jianxun, Yu Tao
Clinical Laboratory, Central Laboratory, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao 266000, People's Republic of China.
Department of Vascular Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong 250021, People's Republic of China.
Pharmacol Res. 2023 Oct;196:106932. doi: 10.1016/j.phrs.2023.106932. Epub 2023 Sep 20.
Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo, we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD.
主动脉夹层(AD)对临床医生来说是一项医学挑战。在此,为了确定新型小非编码piRNA-823(piR-823)在AD中的作用,我们使用了来自AD患者的小鼠和人主动脉。在AD患者中发现piR-823表达水平较高。通过在体外和体内进行功能丧失和功能获得实验,我们探究了piR-823对血管平滑肌细胞(VSMC)和AD的调节作用。无论有无尼古丁处理,piR-823都能明显促进VSMC的增殖、迁移和表型转化。piR-823直接结合并抑制组蛋白去乙酰化酶1(HDAC1)的表达,并通过H3K9ac和H3K27ac调节组蛋白3(H3)的乙酰化,最终影响VSMC功能和AD。为了巩固我们的发现,我们构建了AD小鼠模型,并观察到piR-823拮抗剂通过调节血管重塑强烈抑制AD的发病机制。因此,我们的研究为尼古丁诱导的AD的预防和治疗策略找到了一个潜在靶点。