Deletion of resistin-like molecule-beta attenuates angiotensin II-induced abdominal aortic aneurysm

In the present study, we want to test whether deletion of resistin-like molecule-beta (RELM beta) attenuates angiotensin II (Ang II)-induced formation of abdominal aortic aneurysm (AAA). RELM beta 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 RELM beta (si-RELM beta) groups (n = 15 each), and mice in the last three groups underwent Ang II infusion for 4 weeks to induce AAA. RELM beta gene deficiency significantly decreased AAA incidence and severity, which was associated with reduced macrophage accumulation and decreased expression of proinflammatory cytokines (monocyte chemoattractant protein 1 and interleukin 6), matrix metalloproteinase 2 (MMP-2) and MMP-9 in the aortic wall. In cultured macrophages, RELM beta deficiency blunted the response of macrophages to Ang II and downregulated the levels of proinflammatory cytokines, MMP-2 and MMP-9. Recombinant RELM beta 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 RELM beta 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 RELM beta secretion may be a novel approach for anti-aneurysm treatment.