Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
J Biol Regul Homeost Agents. 2018 May-Jun;32(3):506-516.
miR-145 is highly expressed in vascular cells, where it regulates phenotypic switching and vascular homeostasis, but its role in carotid artery stenosis (CAS) is controversial. In the present study, the expression of miR-145 was assessed by real time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in human samples (both plasma and/or endarterectomy samples) from patients with symptomatic CAS and in controls without CAS. The mouse carotid artery ligation (CAL) model was used to determine the role of miR-145 on vascular smooth muscle cells in vivo (VSMCs) by using a mimic of or an inhibitor of miR-145. We found that miR-145 expression was significantly reduced in the plasma and plaque from patients with CAS (p less than 0.01). The expression of miR-145 in the mouse CAL model, as assessed by qRT-PCR, was significantly reduced compared to the carotid arteries of the control group (p less than 0.01). In vitro, enhancement or inhibition of miR-145 in VSMCs demonstrated that miR-145 significantly inhibited proliferation of VSMCs (p less than 0.05); in vivo, enhancement of miR-145 significantly inhibited neointimal formation in the CAL model (p less than 0.01). These results demonstrate that the expression of miR-145 is reduced in human CAS, miR-145 plays a critical role in CAS by modulation of VSMC proliferation, suggesting that MiR-145 may present a potential therapeutic option for treating CAS.
miR-145 在血管细胞中高度表达，在那里它调节表型转换和血管稳态，但它在颈动脉狭窄（CAS）中的作用是有争议的。在本研究中，通过实时定量逆转录聚合酶链反应（qRT-PCR）评估了 miR-145 在有症状 CAS 患者的人样本（血浆和/或内膜切除术样本）和无 CAS 的对照中的表达。使用 miR-145 的模拟物或抑制剂，通过小鼠颈动脉结扎（CAL）模型在体内确定 miR-145 对血管平滑肌细胞（VSMCs）的作用。我们发现，miR-145 在 CAS 患者的血浆和斑块中的表达明显降低（p 小于 0.01）。通过 qRT-PCR 评估，小鼠 CAL 模型中 miR-145 的表达与对照组的颈动脉相比明显降低（p 小于 0.01）。在体外，VSMCs 中 miR-145 的增强或抑制表明 miR-145 显著抑制了 VSMCs 的增殖（p 小于 0.05）；在体内，miR-145 的增强显著抑制了 CAL 模型中的新生内膜形成（p 小于 0.01）。这些结果表明，miR-145 在人类 CAS 中的表达降低，miR-145 通过调节 VSMC 增殖在 CAS 中发挥关键作用，表明 MiR-145 可能为治疗 CAS 提供一种潜在的治疗选择。
