國家衛生研究院 NHRI:Item 3990099045/10308

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Title:	Vascular smooth muscle cell-related microRNAs are up-regulated in human venous intimal hyperplasia of dialysis patients
Authors:	Wu, CC;Chen, LJ;Hsieh, MY;Lin, TJ;Chiu, JJ
Contributors:	Institute of Cellular and Systems Medicine
Abstract:	Background: Venous intimal hyperplasia is a signiﬁcant problem of vein grafts, especially vascular accesses of dialysis patients. Highly increased vascular smooth muscle cell (VSMC) proliferative activity was demonstrated in stenotic veins but the molecular mechanisms are poorly understood. Recent animal studies demonstrated that microRNAs (miRNAs) are involved in control of proliferation and differentiation of VSMC. Nonetheless, translational evidence supporting the role of VSMC-related miRNAs in human venous intimal hyperplasia is rare. Purpose: To address the role of VSMC-related miRNAs in venous intimal hyper-plasia of dialysis patients Method: Vein grafts tissues were obtained from surgical revision of eight patients with failed dialysis accesses. Control veins were obtained from the same patients at new access creations. Six VSMC-related miRNAs, miR-21, 130a, 133, 145, 221, and 222 were selected according to previous studies in rat carotid arteries. Both quantitative analysis and in-situ hybridization were performed. To prospectively conﬁrm the pathological ﬁndings, 15 patients with early restenosis (less than 3 months) and 15 with late restenosis (beyond 6 months) were invited as the validation cohort. Debris gathered during percutaneous transluminal angioplasty was obtained by Filter wire for quantitative miRNA analysis. Vascular events were prospectively followed for three months. Results: In the derivation cohort, the expressions of miR-21, 130a and 221 in tissues of stenotic vein grafts were signiﬁcantly upregulated. In situ hybridization showed that miR-21 was aberrantly localized in neointima of stenotic veins, less prominent in non-signiﬁcantly stenotic veins and totally absent in control veins. The expression of miR-145 was on the contrary to that of miR-21, i.e., aberrantly localized in normal veins but nearly absent in stenotic veins. In the validation cohort of 30 patients with dysfunctional vascular accesses, the levels of miR-21, 130a and 221 measured in the embolic debris were signiﬁcantly higher in the early restenosis group. Kaplan-Meier plots also showed better restenosis-free patency in patients with low miR-21 levels of embolic debris (p=0.04). Conclusion: Our results provide the ﬁrst translational evidence in human that VSMC-related miRNAs are up-regulated in venous intimal hyperplasia of dialysis patients.
Date:	2016-08
Relation:	European Heart Journal. 2016 Aug;37(Suppl. 1):640.
Link to:	https://doi.org/10.1093/eurheartj/ehw433
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0195-668X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000383869503128
Appears in Collections:	[Jeng-Jiann Chiu ] Conference Papers/Meeting Abstract

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