國家衛生研究院 NHRI:Item 3990099045/11016
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    題名: Induction of microRNA-10a using retinoic acid receptor-alpha and retinoid x receptor-alpha agonists inhibits atherosclerotic lesion formation
    其他題名: Induction of microRNA-10a using retinoic acid receptor-α and retinoid x receptor-α agonists inhibits atherosclerotic lesion formation
    作者: Lee, DY;Yang, TL;Huang, YH;Lee, CI;Chen, LJ;Shih, YT;Wei, SY;Wang, WL;Wu, CC;Chiu, JJ
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: BACKGROUND AND AIMS: MicroRNA (miR)-10a is a shear-regulated miR with the lowest expression in vascular endothelial cells (ECs) in athero-susceptible regions with oscillatory shear stress (OS). The aim of this study is to elucidate the relationship between EC miR-10a and atherosclerosis and develop a hemodynamics-based strategy for atherosclerosis treatment. METHODS: A combination of in vitro flow system and in vivo experimental animals was used to examine the functional roles of EC miR-10a and its clinical applications in atherosclerosis. RESULTS: En face staining showed that EC miR-10a is down-regulated in the inner curvature (OS region) of aortic arch in rats. Co-administration with retinoic acid receptor-alpha (RARalpha)- and retinoid X receptor-alpha (RXRalpha)-specific agonists rescued EC miR-10a expression in this OS region. These effects of OS and RARalpha/RXRalpha-specific agonists on EC miR-10a expression were confirmed by the in vitro flow system, and were modulated by the RARalpha-histone deacetylases complex, with the consequent modulation in the downstream GATA6/vascular cell adhesion molecule (VCAM)-1 signaling cascade. Animal studies showed that miR-10a levels are decreased in both aortic endothelium of atherosclerotic lesions and blood plasma from apolipoprotein E-deficient (ApoE(-/-)) mice. In vivo induction of EC miR-10a by administration of RARalpha/RXRalpha-specific agonists protects ApoE(-/-) mice from atherosclerosis through inhibition of GATA6/VCAM-1 signaling and inflammatory cell infiltration. CONCLUSIONS: Our findings indicate that down-regulation of miR-10a in aortic endothelium and blood serum is associated with atherosclerosis, and miR-10a has potential to be developed as diagnostic molecule for atherosclerosis. Moreover, EC miR-10a induction by RARalpha/RXRalpha-specific agonists is a potential hemodynamics-based strategy for atherosclerosis treatment.
    日期: 2018-02-08
    關聯: Atherosclerosis. 2018 Feb 8;271:36-44.
    Link to: http://dx.doi.org/10.1016/j.atherosclerosis.2018.02.010
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0021-9150&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000428090400005
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85042224951
    顯示於類別:[裘正健] 期刊論文

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