piRNA-823 is a novel potential therapeutic target in aortic dissection

• Published in: Pharmacological research 2023-10, Vol.196, p.106932-106932, Article 106932
• Main Authors: Li, Min, Li, Gang, Yang, Yanyan, Zong, Jinbao, Fu, Xiuxiu, Htet, Aung Lynn Htet, Li, Xiaolu, Li, Tianxiang, Wang, Jianxun, Yu, Tao
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; Aorta - metabolism; Aorta - pathology; Aortic dissection; Aortic Dissection - chemically induced; Aortic Dissection - genetics; Aortic Dissection - metabolism; Aortic Dissection - pathology; Cell Proliferation; Cells, Cultured; Humans; Mice; Myocytes, Smooth Muscle - metabolism; Nicotine - pharmacology; piR-823; Piwi-Interacting RNA - antagonists & inhibitors; Piwi-Interacting RNA - genetics; Piwi-Interacting RNA - metabolism; Vascular remodelling; Vascular smooth muscle cells
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2023.106932

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. [Display omitted]