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白细胞介素-17A:高血压的可能介质和治疗靶点。

Interleukin-17A: Possible mediator and therapeutic target in hypertension.

机构信息

Laboratorio de Patología Renal y Vascular, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, España; Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III, Madrid, España.

Renal, Vascular and Diabetes Research Laboratory, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, España; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Instituto de Salud Carlos III, Madrid, España.

出版信息

Nefrologia (Engl Ed). 2021 May-Jun;41(3):244-257. doi: 10.1016/j.nefro.2020.11.009. Epub 2021 Mar 26.

Abstract

Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 lymphocytes and γδ lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and target organ damage. Studies in mice have shown that IL-17A increases blood pressure, probably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are already elevated in patients with mild or moderate hypertension. Preclinical studies on arterial hypertension have detected IL-17A-producing cells in target organs such as the heart, vessels and kidneys. Patients with hypertensive nephrosclerosis show kidney infiltration by Th17 lymphocytes and γδ lymphocytes that express IL-17A. In addition, in experimental models of hypertension, blocking IL-17A by genetic strategies, or using neutralising antibodies, lowers blood pressure by acting on the vascular wall and tubule sodium transport and reduces damage to target organs. As a whole, the data presented in this review suggest that IL-17A participates in the regulation of blood pressure and in the genesis and maintenance of arterial hypertension, and may constitute a therapeutic target in the future.

摘要

白细胞介素-17A(IL-17A)是一种由免疫系统细胞产生的促炎细胞因子,主要由 Th17 淋巴细胞和 γδ 淋巴细胞产生。本文综述了 IL-17A 在高血压发病机制和靶器官损伤中的作用。小鼠研究表明,IL-17A 通过多种途径升高血压。此外,轻度或中度高血压患者的 IL-17A 血浆浓度已经升高。在动脉高血压的临床前研究中,已经在心脏、血管和肾脏等靶器官中检测到产生 IL-17A 的细胞。高血压性肾硬化症患者的肾脏浸润有表达 IL-17A 的 Th17 淋巴细胞和 γδ 淋巴细胞。此外,在高血压的实验模型中,通过遗传策略阻断 IL-17A 或使用中和抗体,通过作用于血管壁和肾小管钠转运来降低血压,并减少靶器官损伤。综上所述,本文综述的资料表明,IL-17A 参与血压的调节以及动脉高血压的发生和维持,并且可能成为未来的治疗靶点。

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