國家衛生研究院 NHRI:Item 3990099045/8553

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Title:	Flow mediation of endothelial-smooth muscle cell interaction through microRNAs
Authors:	Chen, LJ;Lee, CI;Lin, TE;Chiu, JJ
Contributors:	Institute of Cellular and Systems Medicine
Abstract:	In atherosclerotic lesions, synthetic smooth muscle cells (sSMCs) induce aberrant microRNA (miR) profiles in endothelial cells (ECs) under flow stagnation. Increase in shear stress results in favorable miR modulation to mitigate sSMC-induced inflammation. The objective of this study was to address the role of miRs in sSMC-induced EC inflammation and its inhibition by shear stress. Co-culturing ECs with sSMCs under static condition caused initial increases of four anti-inflammatory miRs (146a/708/451/98) in ECs followed by decreases below the basal levels at 7 days; the increases for miR-146a/708 peaked at 24 h and those for miR-451/98 lasted for only 6-12 h. Shear stress (12 dynes/cm2) to ECs co-cultured with sSMCs for 24 h augments the expression of these four miRs. In vivo, these four miRs are not expressed in neointimal ECs in injured arteries under flow stagnation, but become highly expressed under physiological levels of flow. MiR-146a, -708, -451, and -98 target interleukin (IL)-1 receptor-associated kinase, inhibitor of nuclear factor-κB (NF-κB) kinase subunit-γ, IL-6 receptor, and conserved helix-loop-helix ubiquitous kinase, respectively, to inhibit NF-κB signaling, which exerts negative feedback control on the biogenesis of these miRs. Shear-induction of these miRs in co-cultured ECs is regulated by β1 and β3 integrins. NF-E2-related factor-2 is critical for shear-induction of miR-146a in co-cultured ECs. Lentivirus carrying miR-146a inhibits neointimal formation of mouse carotid arteries induced by blood flow cessation. Our findings indicate that the expressions of miR-146a/708/451/98 are augmented by atheroprotective shear stress in ECs co-cultured with sSMCs to inhibit neointimal lesion formation of injured arteries.
Date:	2014-04
Relation:	FASEB Journal. 2014 Apr;28(1, Suppl.):Article number 696.4.
Link to:	http://www.fasebj.org/content/28/1_Supplement/696.4
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0892-6638&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000346646703269
Appears in Collections:	[Jeng-Jiann Chiu ] Conference Papers/Meeting Abstract

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