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Post-Transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset

  • Qi, You-Fei (Department of Vascular Surgery, the Second Xiang-ya Hospital, Central South University) ;
  • Shu, Chang (Department of Vascular Surgery, the Second Xiang-ya Hospital, Central South University) ;
  • Xiao, Zhan-Xiang (Department of Vascular Surgery, Hainan General Hospital) ;
  • Luo, Ming-Yao (Center of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Fang, Kun (Center of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College) ;
  • Guo, Yuan-Yuan (Department of Vascular Surgery, Fuwai Yunnan Cardiovascular Hospital) ;
  • Zhang, Wen-Bo (Department of Vascular Surgery, Hainan General Hospital) ;
  • Yue, Jie (Department of Vascular Surgery, Hainan General Hospital)
  • Received : 2017.09.09
  • Accepted : 2017.12.21
  • Published : 2018.03.31

Abstract

Aortic dissection (AD) is a catastrophic disease with high mortality and morbidity, characterized with fragmentation of elastin and loss of smooth muscle cells. Although AD has been largely attributable to polymorphisms defect in the elastin-coding gene, tropoelastin (TE), other undermined factors also appear to play roles in AD onset. Here, we investigated the effects of post-transcriptional control of TE by microRNAs (miRNAs) on elastin levels in aortic smooth muscle cells (ASMC). We found that miR-144-3p is a miRNA that targets TE mRNA in both human and mouse. Bioinformatics analyses and dual luciferase reporter assay showed that miR-144-3p inhibited protein translation of TE, through binding to the 3'-UTR of the TE mRNA. Interestingly, higher miR-144-3p levels and lower TE were detected in the ASMC obtained from AD patients, compared to those from non-AD controls. In a mouse model for human AD, infusion of adeno-associated viruses (serotype 6) carrying antisense for miR-144-3p (asmiR-144-3p) under CAG promoter significantly reduced the incidence and severity of AD, seemingly through enhancement of TE levels in ASMC. Thus, our data suggest an essential role of miR-144-3p on the pathogenesis of AD.

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