[心血管疾病与微生物抗原之间的分子模拟]。

Andrés Sánchez-Caraballo, Valentina García-Solano, Sonia Karina González-Rangel, Valeria Grattz-Lamadrid, Marlon Munera-Gomez
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引用次数: 0

摘要

导言心血管疾病是遗传和环境相互作用的结果,会影响心脏和血管的完整性。风险因素包括感染。由于病原体蛋白与人类抗原之间的相似性,针对感染病原体的炎症反应是自身免疫性心血管疾病的诱因,因为免疫反应会因分子模拟而产生交叉反应:我们在 Pubmed 和谷歌学术搜索引擎上搜索了与自身免疫性心脏病有关的病原体以及与这些疾病相关的自身抗原 9。使用 PSI-BLAST 进行全局比对,以确定蛋白质之间的同一性。蛋白质的三维结构由 Uniprot 或 NCBI 获得,如果没有找到,则使用瑞士模型服务器通过同源性对结构进行建模。表位预测通过 Ellipro 和免疫表位数据库(IEDB)进行。此外,还使用PYMOL程序对蛋白质进行三维可视化,并对结构中的表位进行定位:结果:共有 10 种心血管蛋白的氨基酸序列与 10 种病原体的抗原有相同之处(30%-88.24%)。肌动蛋白和热休克蛋白(HSP)家族与克鲁兹锥虫、新型隐球菌和沙眼衣原体的同一性较高,分别为 71.47%、88.24% 和 80.61%。其他病原体,如化脓性链球菌、芽孢杆菌、磁螺菌、幽门螺杆菌和肺炎衣原体,呈现出中等程度的一致性,最大值为 65.79%:结论:人类肌动蛋白和 HSP 与细菌、真菌和原生动物等各种微生物的表位具有高度的一致性,这表明分子模拟和交叉反应是动脉粥样硬化、心脏病、风湿病、心肌炎和南美锥虫病的发病机制。需要开展体外和体内工作来证明在硅学分析中获得的结果。
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[Molecular mimic between cardiovascular diseases and microorganism antigens].

Introduction: Cardiovascular diseases are the result of genetic and environmental interaction that conditions the integrity of the heart and blood vessels. Risk factors include infections. The inflammatory response against the infectious agent is a trigger of autoimmune cardiovascular diseases due to the similarity between the pathogen proteins and human antigens, since the immune response can present cross-reactivity caused by molecular mimicry.

Methods: We performed a search for pathogens involved in autoimmune heart diseases and autoantigens 9 associated with these diseases in the Pubmed and Google Scholar search engines. Identity between proteins was performed through global alignments using PSI-BLAST. The 3D structures of the proteins were obtained by Uniprot or NCBI and, if not found, the structure was modeled by homology using the Swiss Model server. Epitope prediction was performed through Ellipro and the Immunological Epitope Database (IEDB). In addition, the PYMOL program was used to visualize proteins in 3D and position the epitopes in the structure.

Results: A total of ten cardiovascular proteins showed identity (30-88,24%) in their amino acid sequences with antigens from 10 pathogens. Actin proteins and heat shock protein (HSP) families had higher levels of identity with Trypanosoma Cruzi, Cryptococcus neoformans, and Chlamydia trachomatis, 71,47%, 88,24%, and 80,61%, respectively. Other pathogens, such as Streptococcus pyogenes, Bacillus sp, Magnetospirillum gryphiswaldense, Helicobacter pylori and Chlamydia pneumoniae, presented a moderate identity with a maximum value of 65,79%.

Conclusion: Human actin and HSPs share a high degree of conservation with epitopes from various microorganisms, such as bacteria, fungi and protozoa, suggesting molecular mimicry and cross-reactivity as a mechanism for the development of atherosclerosis, heart disease rheumatic disease, myocarditis and Chagas heart disease. In vitro and in vivo work is needed to demonstrate the results obtained in the In Silico analysis.

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