Why the study?
Does deletion of RELMβ prevent Angiotensin II-induced abdominal aortic aneurysm in ApoE-/- mice?
Does deletion of RELMβ prevent Angiotensin II-induced abdominal aortic aneurysm in ApoE-/- mice?
Inhibiting RELMβ secretion attenuates Ang II-induced abdominal aortic aneurysm formation in mice, suggesting a potential novel therapeutic target.
Identifies RELMβ as a potential therapeutic target for abdominal aortic aneurysm; leaves open whether.
// Xiao Meng 1 , Kai Zhang 1 , Jing Kong 1 , Long Xu 1 , Guipeng An 1 , Weidong Qin 1 , Jifu Li 1 and Yun Zhang 1 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, 250012, China Correspondence to: Yun Zhang, email: zhangyun@sdu.edu.cn Jifu Li, email: sdulijifu@163.com Keywords: abdominal aortic aneurysm, RELMβ, inflammation, matrix metalloproteinase Received: May 04, 2017 Accepted: October 03, 2017 Published: October 24, 2017 ABSTRACT 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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Meng et al. (2017) studied this question.
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