合肥工业大学陈元利等研究人员合作发现，秋水仙碱通过调节SRF-MYOCD激活和自噬作用，减少新生内膜形成和平滑肌细胞表型转变。2024年12月11日，《中国药理学报》杂志在线发表了这项成果。

研究人员探讨了秋水仙碱在血管内膜增生中的作用。研究人员发现，秋水仙碱显著减少了动物模型中颈动脉结扎后7、14和28天的血管内膜增生，并增加了新生内膜区域中收缩表型平滑肌细胞（SMA阳性细胞）的数量。体外实验表明，秋水仙碱促进了血管平滑肌细胞（VSMC）从增殖表型向收缩表型的转变。此外，秋水仙碱减弱了PDGF-BB诱导的表型转变，并上调了血清反应因子（SRF）和心肌调节因子（MYOCD）的表达。

进一步的分子机制研究揭示，秋水仙碱抑制了叉头框蛋白O3A（FOXO3A）的表达，从而增加了SRF-MYOCD复合物的激活。FOXO3A可与MSX1/2结合，进而抑制SRF-MYOCD和收缩基因的表达。此外，秋水仙碱通过影响由FOXO3A诱导的自噬相关基因（LC3II、p62和Beclin-1）的表达，维持血管稳态并稳定收缩表型。秋水仙碱还抑制了单核细胞/巨噬细胞的浸润和炎症因子的表达。

总之，该研究表明秋水仙碱通过调节FOXO3A介导的SRF-MYOCD激活和自噬作用抑制血管内膜增生，为未来靶向血管闭塞性疾病的治疗方法提供了新见解。

据了解，VSMC表型转变显著促进血管内膜增生。然而，有效的预防和治疗措施尚未找到。秋水仙碱是一种来源于秋水仙（Colchicum autumnale）的生物碱，传统上用于治疗炎症性疾病。其在新生内膜形成中的作用尚不完全清楚。

附：英文原文

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

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

Issue&Volume: 2024-12-11

Abstract: 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 SRFMYOCD 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.

DOI: 10.1038/s41401-024-01438-x

Source: https://www.nature.com/articles/s41401-024-01438-x