Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm
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Xiao Meng1, Kai Zhang1, Jing Kong1, Long Xu1, Guipeng An1, Weidong Qin1, Jifu Li1 and Yun Zhang1
1The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, 250012, China
Yun Zhang, email: [email protected]
Jifu Li, email: [email protected]
Keywords: abdominal aortic aneurysm, RELMβ, inflammation, matrix metalloproteinase
Received: May 04, 2017 Accepted: October 03, 2017 Published: October 24, 2017
In the present study, we want to test whether deletion of resistin-like molecule-beta(RELMβ) attenuates angiotensin II (Ang II)-induced formation of abdominal aortic aneurysm (AAA). RELMβ gene expression was inhibited by siRNA both in vivo and in vitro. Apolipoprotein E-knockout (ApoE−/−) mice were randomly divided into saline, Ang II, siRNA negative control (si-NC) and siRNA RELMβ (si-RELMβ) groups (n=15 each), and mice in the last three groups underwent Ang II infusion for 4 weeks to induce AAA. RELMβ gene deficiency significantly decreased AAA incidence and severity, which was associated with reduced macrophage accumulation and decreased expression of proinflammatory cytokines (chemoattractant protein 1 and interleukin 6), matrix metalloproteinase 2 (MMP-2) and MMP-9 in the aortic wall. In cultured macrophages, RELMβ deficiency blunted the response of macrophages to Ang II and downregulated the levels of proinflammatory cytokines, MMP-2 and MMP-9. Recombinant RELMβ promoted the secretion of proinflammatory cytokines, MMP-2 and MMP-9 in macrophages and activated extracellular signal-regulated kinase 1/2 (ERK1/2)and c-Jun N-terminal kinase (JNK) signaling, which was reversed with pretreatment with inhibitors of ERK1/2 and JNK. Deletion of RELMβ attenuated Ang II-induced AAA formation in ApoE−/− mice. The inherent mechanism may involve the reduced expression of proinflammatory cytokines, MMP-2 and MMP-9, which was mediated by ERK1/2 and JNK activation. Therefore, inhibiting RELMβ secretion may be a novel approach for anti-aneurysm treatment.
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