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内皮细胞 microRNA-483-3p 具有抗高血压作用。

Endothelial MicroRNA-483-3p Is Hypertension-Protective.

机构信息

Translational Medicine Center, Xi'an Chest Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.

Institute of Cardiovascular Science, Translational Medicine Institute, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

出版信息

Oxid Med Cell Longev. 2022 Feb 17;2022:3698219. doi: 10.1155/2022/3698219. eCollection 2022.

Abstract

Hypertension is a high-risk factor for developing coronary heart disease and stroke. Endothelial dysfunction and arterial remodeling can lead to increased vascular wall thickness and arterial stiffness. Previous studies showed that microRNA-483 (miR-483) enhances endothelial cell (EC) function. Here, we investigated the protective role of miR-483 in hypertension. Data collected from two patient cohorts showed that the serum miR-483-3p level was associated with the progression of hypertension and positively correlated with vascular function. In cultured ECs, miR-483 targets a number of endothelial dysfunction-related genes, such as transforming growth factor- (TGF-), connective tissue growth factor (CTGF), angiotensin-converting enzyme 1 (ACE1), and endothelin-1 (ET-1). Overexpression of miR-483-3p in ECs inhibited Ang II-induced endothelial dysfunction, revealed by the decreased expression of TGF-, CTGF, ACE1, and ET-1. Furthermore, miR-483-3p secreted from ECs was taken up by smooth muscle cells (SMCs) via the exosome pathway, which also decreased these genes in SMCs. Additionally, telmisartan could increase the aortic and serum levels of miR-483-3p in hypertension patients and spontaneous hypertension rats (SHR). These findings suggest that miR-483-3p exerts a protective effect on EC function during the onset of hypertension and thus may be considered a potential therapeutic target for hypertension-related cardiovascular diseases.

摘要

高血压是引发冠心病和中风的高危因素。内皮功能障碍和动脉重构可导致血管壁厚度增加和动脉僵硬。先前的研究表明,微小 RNA-483(miR-483)可增强内皮细胞(EC)功能。在这里,我们研究了 miR-483 在高血压中的保护作用。从两个患者队列中收集的数据表明,血清 miR-483-3p 水平与高血压的进展相关,并且与血管功能呈正相关。在培养的 EC 中,miR-483 靶向许多与内皮功能障碍相关的基因,如转化生长因子-(TGF-)、结缔组织生长因子(CTGF)、血管紧张素转换酶 1(ACE1)和内皮素-1(ET-1)。EC 中 miR-483-3p 的过表达抑制了 Ang II 诱导的内皮功能障碍,表现为 TGF-、CTGF、ACE1 和 ET-1 的表达降低。此外,EC 分泌的 miR-483-3p 通过外泌体途径被平滑肌细胞(SMCs)摄取,这也降低了 SMCs 中的这些基因。此外,替米沙坦可增加高血压患者和自发性高血压大鼠(SHR)的主动脉和血清 miR-483-3p 水平。这些发现表明,miR-483-3p 在高血压发生时对 EC 功能具有保护作用,因此可能被视为高血压相关心血管疾病的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aba9/8872655/ca158b40c612/OMCL2022-3698219.001.jpg

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