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

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

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

abdominal aortic aneurysmVSMCssenescencevinpocetineSIRT1

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

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Baotou Medical College,Baotou 014040 Inner Mongolia Autonomous Region,China

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,Beijing 100005,China

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

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

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abdominal aortic aneurysm VSMCs senescence vinpocetine SIRT1

2025

10.1038/s41401-024-01358-w

中国药理学报(英文版)
中科院上海药物研究所

中国药理学报(英文版)

影响因子：0.926
ISSN：1671-4083
年,卷(期)：2025.46(1)