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长链非编码RNA MBNL1-AS1作为老年高血压患者动脉粥样硬化的替代生物标志物,并调节血管平滑肌细胞功能。

LncRNA MBNL1-AS1 functions as an alternative atherosclerosis biomarker in elderly hypertensive patients and regulates vascular smooth muscle cell function.

作者信息

Song Yanxu, Zhu Xingguang, Cai Xiangang, Yu Yinling, Hu Di

机构信息

Department of Medicine, Qingdao University, Qingdao, China.

Department of Cardiovascular Surgery, Shandong Second Provincial General Hospital, Jinan, China.

出版信息

Minerva Cardiol Angiol. 2025 Jun;73(3):258-266. doi: 10.23736/S2724-5683.24.06619-5. Epub 2024 Oct 8.

DOI:10.23736/S2724-5683.24.06619-5
PMID:39377700
Abstract

BACKGROUND

The clinical role of long non-coding RNA (MBNL1-AS1) in diagnosing atherosclerosis (AS) risks of hypertensive patients and the effects of MBNL1-AS1 on vascular smooth muscle cells (VSMCs) triggered by angiotensin II (Ang II) were investigated.

METHODS

The hypertensive patients were recruited to assess MBNL1-AS1 expression. The ROC curve and Spearman analysis was performed for the significance of MBNL1-AS1. Human VSMCs were treated with Ang II (10 mol/L) to establish a hypertensive cell model. MTT and Transwell chamber were used in proliferative and migratory detection of cell models. Targets of MBNL1-AS1 were verified by luciferase activity. Functional enrichment of shared targets of miR-424-5p was researched by GO and KEGG analysis.

RESULTS

An increase of MBNL1-AS1 was observed in patients with increased carotid intima-media thickness (cIMT). MBNL1-AS1 could predict the risk of AS and related to cIMT levels. The knockdown of MBNL1-AS1 mitigated the influence of Ang II on cellular proliferation and migration by inhibiting miR-424-5p. Enrichment analysis corroborated that targets of miR-424-5p were mainly involved in serine/threonine kinase activity, MAPK signaling pathway, and PI3K-Akt signaling pathway.

CONCLUSIONS

MBNL1-AS1/miR-424-5p axis was connected with the progression of AS induced by hypertension.

摘要

背景

研究长链非编码RNA(MBNL1-AS1)在诊断高血压患者动脉粥样硬化(AS)风险中的临床作用以及MBNL1-AS1对血管紧张素II(Ang II)触发的血管平滑肌细胞(VSMC)的影响。

方法

招募高血压患者以评估MBNL1-AS1的表达。对MBNL1-AS1的意义进行ROC曲线和Spearman分析。用Ang II(10 μmol/L)处理人VSMC以建立高血压细胞模型。MTT和Transwell小室用于细胞模型的增殖和迁移检测。通过荧光素酶活性验证MBNL1-AS1的靶点。通过GO和KEGG分析研究miR-424-5p共享靶点的功能富集情况。

结果

在颈动脉内膜中层厚度(cIMT)增加的患者中观察到MBNL1-AS1升高。MBNL1-AS1可以预测AS风险并与cIMT水平相关。敲低MBNL1-AS1通过抑制miR-424-5p减轻了Ang II对细胞增殖和迁移的影响。富集分析证实miR-424-5p的靶点主要参与丝氨酸/苏氨酸激酶活性、MAPK信号通路和PI3K-Akt信号通路。

结论

MBNL1-AS1/miR-424-5p轴与高血压诱导的AS进展相关。

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