Department of Cardiology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China.
Mol Med Rep. 2013 Aug;8(2):407-12. doi: 10.3892/mmr.2013.1538. Epub 2013 Jun 20.
Dysfunction of vascular smooth muscle cells (VSMCs) is key in the pathogenesis of proliferative cardiovascular diseases, including atherosclerosis and post-angioplasty restenosis. However, to date, the molecular mechanisms of this pathological process have not been elucidated. Growing evidence indicates that microRNAs (miRNAs) are a class of novel gene regulators. Recently, miR-146a was shown to be highly expressed in rat balloon-injured vascular walls as well as in peripheral blood mononuclear cells (PBMCs) from patients with acute coronary syndrome (ACS). The aim of the present study was to investigate the role of miR-146a in regulating VSMC fate and the possible underlying mechanisms involved. Our results revealed that the expression of miR‑146a was increased in proliferative VSMCs. Subsequently, we observed that the knockdown of miR‑146a significantly inhibited the proliferative and migratory properties of VSMCs in vitro, while it markedly promoted the apoptotic capacity of VSMCs. In addition, we demonstrated that the protein expression of nuclear factor-κBp65 (NF-κBp65) and the proliferative cell nuclear antigen (PCNA), known as critical transcriptional factors, were downregulated. By contrast, the crucial proapoptotic molecule Bax has been revealed to be upregulated following miR‑146a knockdown. These results support the conclusion that miR-146a is a novel regulator of VSMC fate and may be a new biomarker or therapeutic target for proliferative cardiovascular disease.
血管平滑肌细胞（VSMCs）功能障碍是增殖性心血管疾病（包括动脉粥样硬化和血管成形术后再狭窄）发病机制的关键。然而，迄今为止，这一病理过程的分子机制尚未阐明。越来越多的证据表明，microRNAs（miRNAs）是一类新的基因调控因子。最近，研究表明 miR-146a 在大鼠球囊损伤血管壁以及急性冠状动脉综合征（ACS）患者的外周血单核细胞（PBMCs）中高度表达。本研究旨在探讨 miR-146a 在调节 VSMC 命运中的作用及其可能涉及的潜在机制。我们的研究结果表明，miR-146a 在增殖性 VSMCs 中的表达增加。随后，我们观察到 miR-146a 的敲低显著抑制了体外 VSMCs 的增殖和迁移能力，而显著促进了 VSMCs 的凋亡能力。此外，我们证实了核因子-κBp65（NF-κBp65）和增殖细胞核抗原（PCNA）的蛋白表达（作为关键转录因子）下调。相反，关键的促凋亡分子 Bax 被证明在 miR-146a 敲低后上调。这些结果支持了 miR-146a 是 VSMC 命运的新调节因子的结论，并且可能是增殖性心血管疾病的新生物标志物或治疗靶点。
