Downregulated microRNA-224 aggravates vulnerable atherosclerotic plaques and vascular remodeling in acute coronary syndrome through activation of the TGF-beta/Smad pathway

作者：Xu, Hai-Ming; Sui, Feng-Hua; Sun, Mei-Hua; Guo, Gong-Liang^*

来源：Journal of Cellular Physiology, 2019, 234(3): 2537-2551.

DOI：10.1002/jcp.26945

• acute coronary syndrome
• microRNA-224
• TGF-beta/Smad pathway
• vascular remodeling
• vulnerable atherosclerotic plaque

Recent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR-224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF-beta/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR-224 inhibitor was prepared for investigating the effect of downregulated miR-224 on the contents of nitric oxide (NO) and endothelin-1 (ET-1), blood lipid levels and inflammatory factor levels in serum as well as the TGF-beta/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high-density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET-1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM-1 and MMP-2 protein expression, TGF-beta, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF-beta/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR-224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF-beta/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.

• 出版日期2019-3
• 单位吉林大学