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Current Vascular Pharmacology

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ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

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Research Article

MiR-199a-5p Deficiency Promotes Artery Restenosis in Peripheral Artery Disease by Regulating ASMCs Function via Targeting HIF-1α and E2F3

Author(s): Duan Liu, Yexiang Jing, Guiyan Peng, Litai Wei, Liang Zheng, Guangqi Chang* and Mian Wang*

Volume 22, Issue 5, 2024

Published on: 21 June, 2024

Page: [342 - 354] Pages: 13

DOI: 10.2174/0115701611280634240616062413

Price: $65

Abstract

Background: Restenosis (RS) poses a significant concern, leading to recurrent ischemia and the potential for amputation following intraluminal angioplasty in the treatment of Peripheral Artery Disease (PAD). Through microRNA microarray analysis, the study detected a significant downregulation of miR-199a-5p within arterial smooth muscle cells (ASMCs) associated with RS.

Objective: This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS.

Methods: Primary ASMCs were extracted from the femoral arteries of both healthy individuals and patients with PAD or RS. The expression levels of miR-199a-5p were assessed using both qRT-PCR and in situ hybridization techniques. To examine the impacts of miR-199a-5p, a series of experiments were performed, including flow cytometry, TUNEL assay, EdU assay, CCK8 assay, Transwell assay, and wound closure assay. A rat carotid balloon injury model was employed to elucidate the mechanism through which miR-199a-5p mitigated neointimal hyperplasia.

Results: MiR-199a-5p exhibited downregulation in RS patients and was predominantly expressed within ASMCs. Elevated the expression of miR-199a-5p resulted in an inhibitory effect of proliferation and migration in ASMCs. Immunohistochemistry and a dual-luciferase reporter assay uncovered that RS exhibited elevated expression levels of both HIF-1α and E2F3, and they were identified as target genes regulated by miR-199a-5p. The co-transfection of lentiviruses carrying HIF-1α and E2F3 alongside miR-199a-5p further elucidated their role in the cellular responses mediated by miR-199a-5p. In vivo, the delivery of miR-199a-5p via lentivirus led to the mitigation of neointimal formation following angioplasty, achieved by targeting HIF-1α and E2F3.

Conclusion: MiR-199a-5p exhibits promise as a prospective therapeutic target for RS since it alleviates the condition by inhibiting the proliferation and migration of ASMCs via its regulation of HIF-1α and E2F3.

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