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

Min Li, Gang Li, Yanyan Yang, Jinbao Zong, Xiuxiu Fu, Htet Aung, Xiaolu Li, Tianxiang Li, Jianxun Wang, Tao Yu

2023Pharmacological Research29 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

HDAC1Histone deacetylaseCancer researchHDAC3Gene silencingVascular smooth muscleCell biologyHistone deacetylase 5ChemistryAcetylationPathogenesisHistoneIn vivoBiologyEndocrinologyImmunologyGeneBiochemistrySmooth muscleGeneticsMicroRNA in disease regulationRNA modifications and cancerCircular RNAs in diseases