摘要
Background Abdominal aortic aneurysm(AAA)is a life-threatening vascular disease associated with endothelial cell senescence.Resveratrol(RSV),a natural polyphenol,exerts potent anti-senescent and anti-inflammatory effects.However,its molecular mechanism in treating AAA remains unclear.Methods An AAA model was established in mice via angiotensin Ⅱ(AngⅡ)infusion[1000 ng/(kg·min)],with a subset receiving RSV treatment[100 mg/(kg·day)by gavage].Aortic diameter was measured,and histopathological changes were assessed by Hematoxylin-Eosin(HE)and Elastica Van Gieson(EVG)staining.Vascular aging was evaluated by senescence-associatedβ-galactosidase(SA-β-gal)activity and pulse wave velocity(PWV).In vitro,human umbilical vein endothelial cells(HUVECs)were treated with AngⅡ(10-6 M)with or without RSV(40μM)and/or the sirtuin 1(SIRT1)inhibitor EX527(10μM).Senescence markers,senescence-associated secretory phenotype(SASP)factor expression[interleukin-1 beta(IL-1β),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)],and SIRT1/p21 pathway proteins were analyzed.Results In vivo,RSV significantly attenuated Ang Ⅱ-induced AAA formation,reducing aortic diameter,preserving elastic fiber integrity,and suppressing vascular senescence and stiffness.In HUVECs,Ang Ⅱ-induced senescence and SASP expression were markedly inhibited by RSV.However,these protective effects were abolished by EX527.Mechanistically,RSV reversed the Ang Ⅱ-induced downregulation of SIRT1 and upregulation of p21,which was also blocked by SIRT1 inhibition.Conclusions RSV effectively prevented experimental AAA formation by alleviating vascular aging and endothelial cell senescence.This protective effect was abrogated by the SIRT1 inhibitor EX527,confirming that RSV mitigated AAA development and vascular senescence through the SIRT1/p21 signaling pathway.These findings highlighted RSV as a promising therapeutic candidate for AAA treatment.
基金
supported by the grant from the Fujian Province Natural Science Foundation(No.2024J01608)。
