Handari Saskia Dyah, Rohman Mohammad Saifur, Sargowo Djanggan, Nugraha Ricardo Adrian, Lestari Bayu, Oceandy Delvac
Doctoral Program of Medical Science, Faculty of Medicine, Brawijaya University, Malang 65145, Indonesia.
Medical Faculty, Ciputra University Surabaya, Surabaya 60271, Indonesia.
J Clin Med. 2024 Aug 7;13(16):4619. doi: 10.3390/jcm13164619.
Inflammation plays a critical role in myocardial infarction as a critical process in the development of heart failure, involving the development of cardiac fibrosis. Colchicine is a well-established anti-inflammatory drug, but its scientific application in controlling post-acute myocardial infarction (AMI) inflammatory processes has not been established. IL-10 is a key cytokine in modulating inflammatory responses, underscoring its potential as a crucial therapeutic target of colchicine. The objective was to explore the protective role of IL-10 modulated by colchicine in myocardial healing and repair following AMI, particularly cardiac fibrosis. The predicted protein of colchicine was assessed using WAY2DRUG PASS as probability active value. Proteins associated with colchicine, cardiac fibrosis, and acute myocardial infarction were analyzed with DisGeNET and Open Target databases. Analysis and visualization of protein-protein interactions were conducted using STRING and Cytoscape. A 3T3 cell line treated with CoCl was used to mimic hypoxic. HIF-1α and IL-10 expression were measured by flow cytometry and analyzed using a one-way ANOVA test. This observational clinical trial examined acute myocardial infarction patients undergoing immediate and delayed primary percutaneous coronary interventions. Subjects were randomized into control groups receiving placebo and intervention groups treated with colchicine. Assessments occurred at 24 h and five days after the intervention. IL-10 expression in the clinical trial was measured by ELISA and analyzed using a -test. Colchicine demonstrates promising bioactivity in treating acute myocardial infarction, with notably activity values highlighting its probable role as a tubulin antagonist (0.744), beta-tubulin antagonist (0.673), and NOS2 inhibitor (0.529). Its primary action targets IL-10, with the protein-protein interactions analysis indicating interactions between IL-10 and key inflammatory mediators-IL-1β, IFN-γ, CCL2, TNF, and TGF-β1-during acute myocardial infarction and cardiac fibrosis. Hypoxic conditions in the CoCl-induced 3T3 cell model show significantly elevated HIF-1α compared to controls ( < 0.0001). Colchicine use significantly increased IL-10 expression in CoCl-treated cells ( < 0.0001) and in AMI patients within five days ( < 0.05). Colchicine may bolster the anti-inflammatory response post-myocardial infarction by activating IL-10 pathways in fibroblasts and in clinical settings, potentially reducing inflammation after AMI. Further investigation into broader aspects of this pathway, particularly in cardiac fibroblasts, is required.
炎症在心肌梗死中起着关键作用，是心力衰竭发展过程中的一个关键过程，涉及心脏纤维化的发展。秋水仙碱是一种公认的抗炎药物，但其在控制急性心肌梗死（AMI）后炎症过程中的科学应用尚未确立。白细胞介素-10（IL-10）是调节炎症反应的关键细胞因子，突出了其作为秋水仙碱关键治疗靶点的潜力。目的是探讨秋水仙碱调节的IL-10在AMI后心肌愈合和修复，特别是心脏纤维化中的保护作用。使用WAY2DRUG PASS评估秋水仙碱的预测蛋白作为概率活性值。使用DisGeNET和Open Target数据库分析与秋水仙碱、心脏纤维化和急性心肌梗死相关的蛋白质。使用STRING和Cytoscape进行蛋白质-蛋白质相互作用的分析和可视化。用CoCl处理的3T3细胞系用于模拟缺氧。通过流式细胞术测量缺氧诱导因子-1α（HIF-1α）和IL-10的表达，并使用单向方差分析进行分析。这项观察性临床试验检查了接受即刻和延迟直接经皮冠状动脉介入治疗的急性心肌梗死患者。受试者被随机分为接受安慰剂的对照组和接受秋水仙碱治疗的干预组。在干预后24小时和五天进行评估。通过酶联免疫吸附测定（ELISA）测量临床试验中的IL-10表达，并使用t检验进行分析。秋水仙碱在治疗急性心肌梗死方面显示出有前景的生物活性，其显著的活性值突出了其作为微管蛋白拮抗剂（0.744）、β-微管蛋白拮抗剂（0.673）和一氧化氮合酶2（NOS2）抑制剂（0.529）的可能作用。其主要作用靶点是IL-10，蛋白质-蛋白质相互作用分析表明在急性心肌梗死和心脏纤维化期间IL-10与关键炎症介质白细胞介素-1β（IL-1β）、干扰素-γ（IFN-γ）、趋化因子配体2（CCL2）、肿瘤坏死因子（TNF）和转化生长因子-β1（TGF-β1）之间存在相互作用。与对照组相比，CoCl诱导的3T3细胞模型中的缺氧条件显示HIF-1α显著升高（P<0.0001）。使用秋水仙碱显著增加了CoCl处理细胞中的IL-10表达（P<0.0001）以及AMI患者在五天内的IL-10表达（P<0.05）。秋水仙碱可能通过激活成纤维细胞中的IL-10途径以及在临床环境中增强心肌梗死后的抗炎反应，潜在地减轻AMI后的炎症。需要对该途径的更广泛方面，特别是在心脏成纤维细胞中进行进一步研究。
