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白细胞介素-9 缺失通过 STAT3 通路缓解血管功能障碍并降低血管紧张素 II 处理的小鼠的血压。

Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice.

机构信息

Department of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, China.

出版信息

Mediators Inflamm. 2020 Feb 14;2020:5741047. doi: 10.1155/2020/5741047. eCollection 2020.

Abstract

BACKGROUND

Multiple interleukin (IL) family members were reported to be closely related to hypertension. We aimed to investigate whether IL-9 affects angiotensin II- (Ang II-) induced hypertension in mice.

METHODS

Mice were treated with Ang II, and IL-9 expression was determined. In addition, effects of IL-9 knockout (KO) on blood pressure were observed in Ang II-infused mice. To determine whether the effects of IL-9 on blood pressure was mediated by the signal transducer and activator of the transcription 3 (STAT3) pathway, Ang II-treated mice were given S31-201. Furthermore, circulating IL-9 levels in patients with hypertension were measured.

RESULTS

Ang II treatment increased serum and aortic IL-9 expression in a dose-dependent manner; IL-9 levels were the highest in the second week and continued to remain high into the fourth week after the treatment. IL-9 KO downregulated proinflammatory cytokine expression, whereas it upregulated anti-inflammatory cytokine levels, relieved vascular dysfunction, and decreased blood pressure in Ang II-infused mice. IL-9 also reduced smooth muscle 22 (SM22 (SM22.

CONCLUSIONS

IL-9 KO alleviates inflammatory response, prevents phenotypic transformation of smooth muscle, reduces vascular dysfunction, and lowers blood pressure via the STAT3 pathway in Ang II-infused mice. IL-9 might be a novel target for the treatment and prevention of clinical hypertension.

摘要

背景

多种白细胞介素(IL)家族成员与高血压密切相关。我们旨在研究白细胞介素 9(IL-9)是否影响小鼠的血管紧张素 II(Ang II)诱导的高血压。

方法

用 Ang II 处理小鼠,并测定 IL-9 的表达。此外,在 Ang II 输注小鼠中观察 IL-9 敲除(KO)对血压的影响。为了确定 IL-9 对血压的影响是否通过信号转导和转录激活因子 3(STAT3)途径介导,用 S31-201 处理 Ang II 处理的小鼠。此外,测量高血压患者的循环 IL-9 水平。

结果

Ang II 处理以剂量依赖性方式增加血清和主动脉中的 IL-9 表达;IL-9 水平在治疗后第二周最高,并持续到第四周。IL-9 KO 下调促炎细胞因子的表达,而上调抗炎细胞因子水平,缓解血管功能障碍,并降低 Ang II 输注小鼠的血压。IL-9 还减少了平滑肌 22(SM22)的表达。

结论

IL-9 KO 通过 Ang II 输注小鼠中的 STAT3 途径减轻炎症反应,防止平滑肌表型转化,减少血管功能障碍,并降低血压。IL-9 可能是治疗和预防临床高血压的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f5/7042522/33d40d23f9a3/MI2020-5741047.001.jpg

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