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

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, effe...

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Main Authors: Yunzhao Yang, Shaoqun Tang, Chunchun Zhai, Xin Zeng, Qingjian Liu, Cheng Xu, Hexiang Chen
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2020/5741047
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author Yunzhao Yang
Shaoqun Tang
Chunchun Zhai
Xin Zeng
Qingjian Liu
Cheng Xu
Hexiang Chen
author_facet Yunzhao Yang
Shaoqun Tang
Chunchun Zhai
Xin Zeng
Qingjian Liu
Cheng Xu
Hexiang Chen
author_sort Yunzhao Yang
collection DOAJ
description 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 22α (SM22α) expression and increased osteopontin (OPN) levels both in mice and in vitro. The effects of IL-9 KO on blood pressure and inflammatory response were significantly reduced by S31-201 treatment. Circulating IL-9 levels were significantly increased in patients with the hypertension group than in the control group, and elevated IL-9 levels positively correlated with both systolic blood pressure and diastolic blood pressure in patients with hypertension. 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.
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spelling doaj-art-0e0cbd1e98d141e2af79a43775803ef92025-08-20T03:54:29ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/57410475741047Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated MiceYunzhao Yang0Shaoqun Tang1Chunchun Zhai2Xin Zeng3Qingjian Liu4Cheng Xu5Hexiang Chen6Department of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, ChinaDepartment of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, ChinaDepartment of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, ChinaDepartment of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, ChinaDepartment of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, ChinaDepartment of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, ChinaDepartment of Anesthesiology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, ChinaBackground. 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 22α (SM22α) expression and increased osteopontin (OPN) levels both in mice and in vitro. The effects of IL-9 KO on blood pressure and inflammatory response were significantly reduced by S31-201 treatment. Circulating IL-9 levels were significantly increased in patients with the hypertension group than in the control group, and elevated IL-9 levels positively correlated with both systolic blood pressure and diastolic blood pressure in patients with hypertension. 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.http://dx.doi.org/10.1155/2020/5741047
spellingShingle Yunzhao Yang
Shaoqun Tang
Chunchun Zhai
Xin Zeng
Qingjian Liu
Cheng Xu
Hexiang Chen
Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice
Mediators of Inflammation
title Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice
title_full Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice
title_fullStr Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice
title_full_unstemmed Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice
title_short Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice
title_sort interleukin 9 deletion relieves vascular dysfunction and decreases blood pressure via the stat3 pathway in angiotensin ii treated mice
url http://dx.doi.org/10.1155/2020/5741047
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