Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway  

作　　者：Hong-qin Yang Zhi-wei Li Xi-xi Dong Jia-xin Zhang Jin Shan Min-jie Wang Jing yang Min-hui Li Jing Wang Hong-mei Zhao 

机构地区：[1]Baotou Medical College,Baotou 014040 Inner Mongolia Autonomous Region,China [2]State Key Laboratory of Complex,Severe,and Rare Diseases,Department of Pathophysiology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences&Peking Union Medical College,Peking Union Medical College Hospital,Bejing 100005,China [3]Medical Experimental Center,School of Basic Medical Sciences,Inner Mongolia Medical University,Chilechuan dairy economic development zone,Hohhot,Inner Mongolia Autonomous Region,Hohhot 010110,China [4]state Key laboratory of Respiratory Health and Multimorbidity,Department of Pathophysiology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China

出　　处：《Acta Pharmacologica Sinica》2025年第1期96-106,共11页中国药理学报(英文版)

基　　金：This study was supported by grants from the National High Level Hospital Clinical Research Funding(2022-PUMCH-D-002);Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences grant,No.2021-12M-1-016;National Key Research and Development Program of China(2021YFE0190100).

摘　　要：Abdominal aortic aneurysm(AAA)is a degenerative disease that caused mortality in people aged>65.Senescence plays a critical role in AAA pathogenesis.Advances in AAA repair techniques have occurred,but a remaining priority is therapies to limit AAA growth and rupture.Our Previous study found cyclic nucleotide phosphodiesterase 1C(PDE1C)exacerbate AAA through aggravate vascular smooth muscle cells(VSMCs)senescence by downregulating Sirtuin1(SiRT1)expression and activity.Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation,it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA.This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice.In addition,the elastin degradation,MMP(matrix metalloproteinase)activity,macrophage infiltration,ROS production,collagen fibers remodeling,and VSMCs senescence were decreased in AAA treated with vinpocetine.While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice.Accordingly,we revealed that vinpocetine suppressed migration,proliferation,and senescence in VSMCs.Moreover,vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy.In conclusion,this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.

关 键 词：abdominal aortic aneurysm VSMCS SENESCENCE VINPOCETINE SIRT1 

分 类 号：R54[医药卫生—心血管疾病]