Min Li1, Yanyan Yang1, Jinbao Zong2, Zhibin Wang3, Shaoyan Jiang4, Xiuxiu Fu3, Xiangqin He3, Xiaoxin Li5, Qianqian Xue5, Jian-Xun Wang1, Tao Yu6. 1. Department of Immunology, School of Basic Medicine, Qingdao University, 266021, People's Republic of China. 2. Clinical Laboratory, Central Laboratory, The Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao 266000, People's Republic of China. 3. Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China. 4. Department of Cardiology, The Affiliated Cardiovascular Hospital of Qingdao University, No. 5 Zhiquan Road, Qingdao 266000, People's Republic of China. 5. Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, 266021, People's Republic of China. 6. Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, People's Republic of China; Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, 266021, People's Republic of China. Electronic address: yutao0112@qdu.edu.cn.
Abstract
BACKGROUND: Aortic dissection (AD) is a lethal cardiac disorder and one of the most concerning cardiovascular diseases (CVDs). Increasing evidence indicates that human aortic vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AD, especially related to phenotypic transformation. And notablely, the development of AD is also accompanied by inflammation. METHODS: By using quantitative real-time PCR and fluorescence in situ hybridization (FISH), we detected the expression levels of miR-564 in vitro and in vivo. The effects of miR-564 proliferation and migration were investigated in VSMCs. The downstream targets of miR-564 were found by bioinformatics analyse, and verified in the regulation on VSMCs. An AD murine model was constructed and clinical evaluation was performed to explore the critical roles of miR-564 in vivo. At the same time, the level of inflammation was detected using quantitative real-time PCR and immunofluorescence. RESULTS: Overexpression of miR-564 inhibited cell proliferation and migration, as well as phenotype switch, with or without platelet-derived growth factor BB (PDGF-BB) treatment, whereas downregulation of miR-564 led to opposite results. Mechanistically, miR-564 directly interacted with the target genes proto-oncogene (SKI) and neurogranin (NRGN) to regulate the biological functions of VSMCs. In particular, animal experiments demonstrated that miR-564 can alleviate the progression of AD mainly through mediating phenotypic swithing and inflammation which was consistent with clinical evaluation. CONCLUSIONS: Our study identified miR-564 as a significant molecule that attenuates AD progression by inhibiting inflammation and VSMCs proliferation, migration and phenotypic transformation, suggesting that it may be a potential therapeutic target for AD.
BACKGROUND: Aortic dissection (AD) is a lethal cardiac disorder and one of the most concerning cardiovascular diseases (CVDs). Increasing evidence indicates that human aortic vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AD, especially related to phenotypic transformation. And notablely, the development of AD is also accompanied by inflammation. METHODS: By using quantitative real-time PCR and fluorescence in situ hybridization (FISH), we detected the expression levels of miR-564 in vitro and in vivo. The effects of miR-564 proliferation and migration were investigated in VSMCs. The downstream targets of miR-564 were found by bioinformatics analyse, and verified in the regulation on VSMCs. An AD murine model was constructed and clinical evaluation was performed to explore the critical roles of miR-564 in vivo. At the same time, the level of inflammation was detected using quantitative real-time PCR and immunofluorescence. RESULTS: Overexpression of miR-564 inhibited cell proliferation and migration, as well as phenotype switch, with or without platelet-derived growth factor BB (PDGF-BB) treatment, whereas downregulation of miR-564 led to opposite results. Mechanistically, miR-564 directly interacted with the target genes proto-oncogene (SKI) and neurogranin (NRGN) to regulate the biological functions of VSMCs. In particular, animal experiments demonstrated that miR-564 can alleviate the progression of AD mainly through mediating phenotypic swithing and inflammation which was consistent with clinical evaluation. CONCLUSIONS: Our study identified miR-564 as a significant molecule that attenuates AD progression by inhibiting inflammation and VSMCs proliferation, migration and phenotypic transformation, suggesting that it may be a potential therapeutic target for AD.