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

Yunzhao Yang,Cheng Xu,Hexiang Chen,Qingjian Liu,Chunchun Zhai,Xin Zeng,Shaoqun Tang

doi:10.1155/2020/5741047

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 22α (SM22α (SM22Conclusions 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.

Highlights

Hypertension is the most common disease in the world, and the total number of people with hypertension is estimated to exceed 1 billion globally [1]
IL-9 KO had no significant effect on systolic blood pressure (SBP) during the first week of Ang II infusion; SBP significantly decreased in IL-9 KO mice from the second week to the fourth week (Figure 2(a))
Results of internal carotid artery invasive measurement showed that the SBP, diastolic blood pressure (DBP), and mean arterial pressure (MAP) decreased significantly after Ang II infusion in IL-9 KO mice (Figures 2(b)–2(d))

Summary

Introduction

Hypertension is the most common disease in the world, and the total number of people with hypertension is estimated to exceed 1 billion globally [1]. Knockout of IL-12p35, the subunit shared by IL12 and IL-35, significantly elevated blood pressure in Ang II-infused mice; treatment with IL-12, a proinflammatory cytokine, rather than the anti-inflammatory cytokine IL35, surprisingly reduced Ang II-induced hypertension in mice [12]. 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. 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. The effects of IL-9 KO on blood pressure and inflammatory response were significantly reduced by S31-201 treatment. 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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Results

Conclusion