期刊
ATHEROSCLEROSIS
卷 271, 期 -, 页码 36-44出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2018.02.010
关键词
Atherosclerosis; Endothelial cell; MicroRNA; Retinoic acid receptor; Shear stress
资金
- Ministry of Science and Technology, Taiwan [MOST-106-2633-B-009-001/105-2321-B-400-007/106-3114-Y-043-021, MOST-103-2321-B-400-011]
- National Health Research Institutes Central Government S T grant [106-1901-01-10-02/106-0324-01-10-07]
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 (RAR alpha)-and retinoid X receptor-alpha (RXR alpha)-specific agonists rescued EC miR-10a expression in this OS region. These effects of OS and RAR alpha/RXR alpha-specific agonists on EC miR-10a expression were confirmed by the in vitro flow system, and were modulated by the RAR alpha-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 RAR alpha/RXR alpha-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 RAR alpha/RXR alpha-specific agonists is a potential hemodynamics-based strategy for atherosclerosis treatment. (C) 2018 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据