Licochalcone A attenuates abdominal aortic aneurysm induced by angiotensin II via regulating the miR‐181b/SIRT1/HO‐1 signaling

Abstract Licochalcone A (LA), a chalcone derived from liquorice, exhibits multiple biological activities, including anti‐oxidation and anti‐inflammation. This study aimed to investigate the role and underlying mechanism of LA in the abdominal aortic aneurysm (AAA). AAA model was established by continuous infusion of 1000 ng/kg/min of angiotensin II (AngII) in ApoE ‐/‐ mice for 4 weeks. At 7 days before AngII administration, 5 mg/kg/day or 10 mg/kg/day of LA was intraperitoneally administered to mice and continued for 4 weeks. The characteristics and quantification of AAAs were determined in situ. Real‐time PCR or western blot was used to measure mRNA or protein levels of matrix metalloproteinase 2 and matrix metalloproteinase 9; pro‐inflammatory cytokines tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6; apoptosis‐related proteins Bax, Bcl‐2, and active caspase‐3; miR‐181b; Sirtuin 1 (SIRT1); and heme oxygenase‐1 (HO‐1). Mouse‐aorta‐origin vascular smooth muscle (MOVAS) cells were used to confirm the involved pathways in vitro. We found LA administration dose‐dependently reduced the incidence of AngII‐induced AAA, aneurysm diameter enlargement, elastin degradation, matrix metalloproteinase production, pro‐inflammatory cytokines and miR‐181b expression, and vascular smooth muscle cell apoptosis. It elevated SIRT1 and HO‐1 expression that was suppressed by AngII. AngII enhanced miR‐181b but reduced SIRT1 and HO‐1 expression in MOVAS cells. In AngII‐stimulated MOVAS cells, downregulation of miR‐181b significantly upregulated the expression of SIRT1 and HO‐1, the effect of which was abrogated by SIRT1 siRNA. Collectively, LA could attenuate AngII‐induced AAA by modulating the miR‐181b/SIRT1/HO‐1 signaling. LA might be a potential medical therapy for small AAA.