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Silencing IL12p35 Promotes Angiotensin II-Mediated Abdominal Aortic Aneurysm through Activating the STAT4 Pathway

Authors :
Lanlan Wang
Chengyun Hu
Yongfei Dong
Feibiao Dai
Yongxia Xu
Yumeng Dai
Lijie Shao
Defa Zhu
Source :
Mediators of Inflammation, Vol 2021 (2021)
Publication Year :
2021
Publisher :
Hindawi Limited, 2021.

Abstract

Background and Purpose. Abdominal aortic aneurysm (AAA) is a chronic inflammatory disorder and the important causes of death among men over the age of 65 years. Interleukin-12p35 (IL12p35) is an inflammatory cytokine that participates in a variety of inflammatory diseases. However, the role of IL12p35 in the formation and development of AAA is still unknown. Experimental Approach. Male apolipoprotein E-deficient (Apoe-/-) mice were generated and infused with 1.44 mg/kg angiotensin II (Ang II) per day. We found that IL12p35 expression was noticeably increased in the murine AAA aorta and isolated aortic smooth muscle cells (SMCs) after Ang II stimulation. IL12p35 silencing promoted Ang II-induced AAA formation and rupture in Apoe-/- mice. IL12p35 silencing markedly increased the expression of inflammatory cytokines, including IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), in both the serum and AAA aorta. Additionally, IL12p35 silencing exacerbated SMC apoptosis in Apoe-/- mice after Ang II infusion. IL12p35 silencing significantly increased signal transducer and activator of transcription (STAT) 4 phosphorylation levels in AAA mice, and STAT4 knockdown abolished the IL12p35-mediated proinflammatory response and SMC apoptosis. Interpretation. Silencing IL12p35 promotes AAA formation by activating the STAT4 pathway, and IL12p35 may serve as a novel and promising therapeutic target for AAA treatment.

Subjects

Subjects :
Pathology
RB1-214

Details

Language :
English
ISSN :
09629351 and 14661861
Volume :
2021
Database :
Directory of Open Access Journals
Journal :
Mediators of Inflammation
Publication Type :
Academic Journal
Accession number :
edsdoj.9cc675e2ba44299284a4494b02accd
Document Type :
article
Full Text :
https://doi.org/10.1155/2021/9450843