基于生物信息学分析急性心肌梗死合并慢性阻塞性肺疾病的关键基因和潜在药物

摘要
图/表
参考文献(25)
相关文章 (15)

全文: PDF (1278 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的基于生物信息学分析急性心肌梗死（AMI）合并慢性阻塞性肺疾病（COPD）的关键基因和潜在药物，为疾病的诊断治疗提供新的生物信息学依据。方法从GEO数据库下载了包含AMI和COPD微阵列信息的3个数据集并筛选差异表达基因（DEG）。对两种疾病共有的差异表达基因进行了GO功能注释、KEGG通路富集分析、Metascape富集分析。然后构建了蛋白质-蛋白质相互作用（PPI）网络识别参与疾病发生发展的关键基因。最后，本研究使用药物-药物基因相互作用数据库来寻找潜在的治疗药物。结果通过对AMI和COPD的3个数据集整合后获得61个DEGs，GO功能注释结果显示其主要涉及炎症反应、碳水化合物和糖皮质激素受体结合。多位于细胞器外膜和颗粒内腔。KEGG、Metascape富集集中于免疫、炎症、凋亡等途径。PPI网络识别的8个关键基因，共筛选了74种可能相关的治疗药物。结核菌素、托马利拉单抗、白藜芦醇己酸、塔斯奎尼德、帕尼莫德与疾病的关联性高。结论鉴定出的基因和通路可能是AMI合并COPD的潜在治疗靶点，为疾病分子机制提供新的依据。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	姜晨阳李烁巢潇莺钟国强

关键词 ：急性心肌梗死, 慢性阻塞性肺疾病, 生物信息学

Abstract：Objective To provide a new bioinformatics basis for the diagnosis and treatment of the disease, we analyzed the key genes and potential drugs of acute myocardial infarction (AMI) complicated with chronic obstructive pulmonary disease (COPD) based on bioinformatics. Methods Three data sets containing AMI and COPD microarray information were downloaded from the GEO database and differentially expressed genes (DEG) were screened. GO function annotation, KEGG pathway enrichment analysis, and Metascape enrichment analysis were performed on the differentially expressed genes shared by the two diseases. Then a protein protein interaction (PPI) network was constructed to identify key genes involved in the occurrence and development of diseases. Finally, the drug-drug gene interaction database was used to find potential therapeutic drugs. Results After integrating the three data sets of AMI and COPD, 61 DEGs were obtained. The results of GO function annotation showed that they were mainly involved in inflammation, carbohydrate and glucocorticoid receptor binding. Mostly located in the outer membrane of organelles and the inner cavity of particles. KEGG and Metascape enrich the pathways such as immune, inflammation, and apoptosis. Eight key genes identified by the PPI network, a total of 74 potentially related therapeutic drugs were screened. Tuberculin, tomalizumab, resveratrol caproic acid, tasquinide, and pannimod were highly associated with diseases. Conclusion The identified genes and pathways may be potential therapeutic targets for AMI combined with COPD, and provide a new basis for the molecular mechanism of the disease.

Key words： Acute myocardial infarction Chronic obstructive pulmonary disease Bioinformatics

基金资助:国家自然科学基金资助项目（82060068）。

通讯作者: 钟国强（1958.3-），男，博士，教授，主任医师；研究方向：心律失常和冠心病的介入治疗。

作者简介: 姜晨阳（1994.12-），男，广西医科大学第一临床医学院2019级心血管内科学专业在读硕士研究生；研究方向：心律失常和冠心病的介入治疗。

引用本文:

姜晨阳李烁巢潇莺钟国强. 基于生物信息学分析急性心肌梗死合并慢性阻塞性肺疾病的关键基因和潜在药物[J]. 中国医药导报, 2021, 18(28): 13-17.
JIANG Chenyang LI Shuo CHAO Xiaoying ZHONG Guoqiang. Analysis of key genes and potential drugs in acute myocardial infarction combined with chronic obstructive pulmonary disease based on bioinformatics. 中国医药导报, 2021, 18(28): 13-17.

链接本文:

https://www.yiyaodaobao.com.cn/CN/ 或 https://www.yiyaodaobao.com.cn/CN/Y2021/V18/I28/13

[1] Ratcovich H，Josiassen J，Helgestad OKL，et al. Incidence，Predictors，and Outcome of In-Hospital Bleeding in Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction [J]. Am J Cardiol，2021，144（3）：13-19.
[2] Benjamin EJ，Blaha MJ，Chiuve SE，et al. Heart Disease and Stroke Statistics-2017 Update：A Report From the American Heart Association [J]. Circulation，2017，135（10）：e146-e603.
[3] Singh D，Long G，Can?觭ado JED，et al. Small airway disease in chronic obstructive pulmonary disease：insights and implications for the clinician [J]. Curr Opin Pulm Med，2020，26（2）：121-125.
[4] Obi J，Mehari A，Gillum R. Mortality Related to Chronic Obstructive Pulmonary Disease and Co-morbidities in the United States，A Multiple Causes of Death Analysis [J]. COPD，2018，15（2）：200-205.
[5] Rothnie KJ，Smeeth L，Herrett E，et al. Closing the mortality gap after a myocardial infarction in people with and without chronic obstructive pulmonary disease [J]. Heart，2015，101（14）：1103-1110.
[6] Sin DD，Anthonisen NR，Soriano JB，et al. Mortality in COPD：Role of comorbidities [J]. Eur Respir J，2006，28（6）：1245-1257.
[7] Su TH，Chang SH，Chen PC，et al. Temporal Trends in Treatment and Outcomes of Acute Myocardial Infarction in Patients With Chronic Obstructive Pulmonary Disease：A Nationwide Population-Based Observational Study [J]. J Am Heart Assoc，2017，6（3）：624-631.
[8] Rothnie KJ，Yan R，Smeeth L，et al. Risk of myocardial infarction （MI） and death following MI in people with chronic obstructive pulmonary disease （COPD）：a systematic review and meta-analysis [J]. BMJ Open，2015，5（9）：78-81.
[9] Muse ED，Kramer ER，Wang H，et al. A Whole Blood Molecular Signature for Acute Myocardial Infarction [J]. Sci Rep，2017，7（1）：122-126.
[10] Heinbockel L，Marwitz S，Schromm AB，et al. Identification of novel target genes in human lung tissue involved in chronic obstructive pulmonary disease [J]. Int J Chron Obstruct Pulmon Dis，2018，13（22）：55-59.
[11] Ezzie ME，Crawford M，Cho JH，et al. Gene expression networks in COPD：microRNA and mRNA regulation [J]. Thorax，2012，67（2）：122-131.
[12] Lin CF，Su CJ，Liu JH，et al. Potential Effects of CXCL9 and CCL20 on Cardiac Fibrosis in Patients with Myocardial Infarction and Isoproterenol-Treated Rats [J]. J Clin Med，2019，8（5）：43-47.
[13] R?觟hrl J，Yang D，Oppenheim JJ，et al. Specific binding and chemotactic activity of mBD4 and its functional orthologue hBD2 to CCR6-expressing cells [J]. J Biol Chem，2010，285（10）：7028-7034.
[14] Safa A，Rashidinejad HR，Khalili M，et al. Higher circulating levels of chemokines CXCL10，CCL20 and CCL22 in patients with ischemic heart disease [J]. Cytokine，2016， 83（1）：47-57.
[15] Demedts IK，Bracke KR，Vanpottelberge G，et al. Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease [J]. Am J Respir Crit Care Med，2007， 175（10）：121-126.
[16] Iwata A，Morgan-stevenson V，Schwartz B，et al. Extracellular BCL2 proteins are danger-associated molecular patterns that reduce tissue damage in murine models of ischemia-reperfusion injury [J]. PLoS One，2010，5（2）：e9103-e9106.
[17] Yang D，Yan Y，Hu F，et al. CYP1B1，VEGFA，BCL2，and CDKN1A affect the Development of Chronic Obstructive Pulmonary Disease [J]. Int J Chron Obstruct Pulmon Dis，2020，15（1）：67-75.
[18] Dejesus NM，Wang L，Lai J，et al. Antiarrhythmic effects of interleukin 1 inhibition after myocardial infarction [J]. Heart rhythm，2017，14（5）：727-736.
[19] Li HL，Zhuo ML，Wang D，et al. Targeted cardiac overexpression of A20 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction [J]. Circulation，2007，115（14）：1885-1894.
[20] Momtazi G，Lambrecht BN，Naranjo JR，et al. Regulators of A20 （TNFAIP3）：new drug-able targets in inflammation [J]. Am J Physiol Lung Cell Mol Physiol，2019，316（3）：L456-L469.
[21] Sheng X，Fan T，Jin X. Identification of Key Genes Involved in Acute Myocardial Infarction by Comparative Transcriptome Analysis [J]. Biomed Res Int，2020，2020（14）：70-81.
[22] Heger LA，Hortmann M，Albrecht M，et al. Inflammation in acute coronary syndrome：Expression of TLR2 mRNA is increased in platelets of patients with ACS [J]. PLoS One，2019，14（10）：e122-e124.
[23] Marinkovi■ G，Koenis DS，Decamp L，et al. S100A9 Links Inflammation and Repair in Myocardial Infarction [J]. Circ Res，2020，127（5）：664-676.
[24] Railwah C，Lora A，Zahid K，et al. Cigarette smoke induction of S100A9 contributes to chronic obstructive pulmonary disease [J]. Am J Physiol Lung Cell Mol Physiol，2020，131（1）：234-241.
[25] Zhao Y，Tian B，Sun H，et al. Pharmacoproteomics reveal novel protective activity of bromodomain containing 4 inhibitors on vascular homeostasis in TLR3-mediated airway remodeling [J]. J Proteomics，2019，205（10）：34-38.