Colchicine reduces neointima formation and VSMC phenotype transition by modulating SRF-MYOCD activation and autophagy  

作　　者：Bu-chun Zhang Wen-ya Zhu Sheng-nan Wang Meng-meng Zhu Hui Ma Liang Dong Xiao-xiao Yang Chuan-rui Ma Li-kun Ma Yuan-li Chen 

机构地区：[1]Department of Cardiology,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,230001,China [2]Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions,Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes,School of Food and Biological Engineering,Hefei University of Technology,Hefei,230601,China [3]First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin,300381,China

出　　处：《Acta Pharmacologica Sinica》2025年第4期951-963,共13页中国药理学报(英文版)

基　　金：supported by the National Natural Science Foundation of China(NSFC)grants(Grant No.U22A20272 to YLC);Anhui Provincial Natural Science Foundation(Grant No.2308085MH240 to YLC,2208085MH196 to BCZ);Pilot Demonstration Project for the Inheritance and Innovative Development of Traditional Chinese Medicine in Nankai District,Tianjin(20240204007 to CRM).

摘　　要：Vascular smooth muscle cell(VSMC)phenotype transformation significantly contributes to vascular intimal hyperplasia.However,effective preventive and therapeutic measures are lacking.Colchicine,a binary alkaloid derived from Colchicum autumnale,is traditionally used for treating inflammatory diseases.Its role in neointima formation is not fully understood.Here,we investigated the role of colchicine in vascular intimal hyperplasia.We found that colchicine significantly reduced vascular intimal hyperplasia in an animal model at 7,14,and 28 days post carotid artery ligation and increased the number of contractile-phenotype VSMCs(SMA-positive cells)in the neointimal areas.In vitro experiments demonstrated that colchicine facilitated the transition of VSMCs from a proliferative phenotype to a contractile phenotype.Additionally,colchicine attenuated PDGF-BB-induced phenotypic conversion and upregulated the expression of serum response factor(SRF)and myocardin(MYOCD).Further molecular mechanistic studies revealed that colchicine inhibited the expression of forkhead box protein O3A(FOXO3A)to increase the activation of the SRF‒MYOCD complex.FOXO3A can bind to MSX1/2,thereby inhibiting the expression of SRF–MYOCD and contractile genes.Moreover,colchicine maintains vascular homeostasis and stabilizes the contractile phenotype by affecting the expression of autophagy-related genes(LC3II,p62,and Beclin-1)induced by FOXO3A.Additionally,colchicine inhibited monocyte/macrophage infiltration and inflammatory cytokine expression.In summary,this study suggests that colchicine inhibits vascular intimal hyperplasia by modulating FOXO3A-mediated SRF-MYOCD activation and autophagy,providing new insights for future therapeutic approaches targeting occlusive vascular diseases.

关 键 词：neointima formation COLCHICINE VSMC FOXO3A AUTOPHAGY 

分 类 号：R543[医药卫生—心血管疾病]