MicroRNA-disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice
MicroRNA-disease Network Analysis Repurposes Methotrexate for the Treatment of Abdominal Aortic Aneurysm in Mice
复制标题
MicroRNA-疾病网络分析重新利用甲氨蝶呤治疗小鼠腹主动脉瘤
DOI：
10.1016/j.gpb.2022.08.002
复制
发表时间：
2024-03-01
影响因子：
9.5
通讯作者：
Cui，Qinghua
中科院分区：
文献类型：
--
作者：
Shen，Yicong;Gao，Yuanxu;Cui，Qinghua
腹主动脉瘤（AAA）是腹主动脉的永久性扩张，具有高度致命性。本研究的主要目的是寻找AAA的非侵入性药物治疗方法，目前尚无有效的药物治疗方法。网络医学代表了一种前沿技术，因为疾病网络的分析和建模可以提供有关特定疾病病因和可能有效的治疗方法的关键线索。在这里，我们提出了一种新的算法来量化疾病关系的基础上积累了大量的microRNA-disease关联数据集，然后建立了一个疾病网络，涵盖15个疾病类别和304种疾病。分析揭示了这些疾病的一些模式。例如，疾病在网络中往往是集群和连贯的。令人惊讶的是，我们发现AAA与类风湿性关节炎和系统性红斑狼疮这两种自身免疫性疾病表现出最强的相似性，这表明AAA可能是一种病因学上的自身免疫性疾病。基于这一观察，我们进一步假设，自身免疫性疾病的药物可以重新用于预防和治疗AAA。最后，动物实验证实，治疗自身免疫性疾病的药物甲氨蝶呤能够减轻AAA的形成和发展。
Abdominal aortic aneurysm(AAA) is a permanent dilatation of the abdominal aorta and is highly lethal. The main purpose of the current study is to search for noninvasive medical therapies for AAA, for which there is currently no effective drug therapy.Network medicinerepresents a cutting-edge technology, as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective. Here, we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases. Analysis revealed some patterns for these diseases. For instance, diseases tended to be clustered and coherent in the network. Surprisingly, we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus, both of which areautoimmune diseases, suggesting that AAA could be one type of autoimmune diseases in etiology. Based on this observation, we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA. Finally, animal experiments confirmed thatmethotrexate, a drug for autoimmune diseases, was able to alleviate the formation and development of AAA.