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

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 22α (SM22α (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.

MeSH terms

  • Adult
  • Aged
  • Angiotensin II / therapeutic use*
  • Animals
  • Blood Pressure / physiology
  • Cells, Cultured
  • Cytokines / blood
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Interleukin-9 / blood*
  • Interleukin-9 / metabolism*
  • Mice
  • Mice, Knockout
  • Middle Aged
  • RNA, Messenger / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism

Substances

  • Cytokines
  • Interleukin-9
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Angiotensin II