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

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机构: [1]Division of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. [2]Division of Vascular Surgery, Xuanwu Hospital, Capital Medical University and Institute of Vascular Surgery, Capital Medical University, Beijing, 100053, China. [3]National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
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关键词: Peripheral Artery Disease Restenosis Arterial Smooth Muscle Cells miR-199a-5p HIF-1α E2F3

摘要:
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.This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS.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.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.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.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

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出版当年[2023]版
大类 | 3 区 医学
小类 | 3 区 外周血管病 3 区 药学
最新[2023]版
大类 | 3 区 医学
小类 | 3 区 外周血管病 3 区 药学
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出版当年[2022]版:
Q2 PERIPHERAL VASCULAR DISEASE Q2 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q2 PERIPHERAL VASCULAR DISEASE Q2 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

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第一作者机构: [1]Division of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. [2]Division of Vascular Surgery, Xuanwu Hospital, Capital Medical University and Institute of Vascular Surgery, Capital Medical University, Beijing, 100053, China.
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通讯机构: [1]Division of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China. [3]National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
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