國家衛生研究院 NHRI:Item 3990099045/10739

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Title:	Hemodynamics-based strategy of using retinoid acid receptor and retinoid X receptor agonists to treat atherosclerotic diseases
Authors:	Chiu, JJ;Lee, DY
Contributors:	Institute of Cellular and Systems Medicine
Abstract:	Aim: MicroRNA-10a (miR-10a) is a miR with the lowest expression in the athero-susceptible regions in normal adult swine. The present study used pathogenic condition to identify the relationship between miR-10a and atherosclerosis, with the goals of developing the clinical application of miR-10a for atherosclerosis. Methods: We combine in vitro flow system, in vivo experimental animals, and human specimens with coronary artery disease (CAD) to examine the functional role of miR-10a and its diagnostic and therapeutic application in atherosclerosis. Results: We find that miR-10a levels in both aortic endothelium of atherosclerotic lesions and blood plasma from ApoE-knockout mice and CAD patients are decreased. The down-regulation of endothelial miR-10a in human atherosclerotic lesions is accompanied by the strong expressions of its downstream molecules GATA6/VCAM-1. The combined usage of RARα- and RXRα-specific agonists exerts additive effects on rescuing oscillatory shear-inhibited miR-10a expression to repress GATA6/VCAM-1 in ECs in vitro. The effect of RARα/RXRα-specific agonists on rescuing miR-10a is confirmed in vivo on rats by en face staining. Induction of endothelial miR-10a in vivo by administrating RARα/RXRα-specific agonists protects ApoE-knockout mice from atherosclerosis through inhibiting GATA6/VCAM-1 and inflammatory cell infiltration in the atherosclerotic vessel wall. The safety of in vivo miR-10a induction is validated by blood chemistry, urine, and mortality rate analyses. Conclusions: Our findings identify that decreased miR-10a levels in aortic endothelium and blood serum are highly related to atherogenesis and have potential to be developed as diagnostic molecule for atherosclerotic disease. Moreover, RARα/RXRα-specific agonists are potential hemodynamics-based components for atherosclerosis treatment.
Date:	2017-08
Relation:	Atherosclerosis. 2017 Aug;263:E50-E51.
Link to:	http://dx.doi.org/10.1016/j.atherosclerosis.2017.06.172
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:000407634000139
Appears in Collections:	[Jeng-Jiann Chiu ] Conference Papers/Meeting Abstract

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