Department of Computer Science and Engineering, Jashore University of Science and Technology, Bangladesh.
Department of Microbiology, Jahangirnagar University, Savar, Dhaka-1342, Bangladesh.
Brief Bioinform. 2021 Mar 22;22(2):1387-1401. doi: 10.1093/bib/bbaa426.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals that have hypertension or cardiovascular comorbidities have an elevated risk of serious coronavirus disease 2019 (COVID-19) disease and high rates of mortality but how COVID-$19$ and cardiovascular diseases interact are unclear. We therefore sought to identify novel mechanisms of interaction by identifying genes with altered expression in SARS-CoV-$2$ infection that are relevant to the pathogenesis of cardiovascular disease and hypertension. Some recent research shows the SARS-CoV-$2$ uses the angiotensin converting enzyme-$2$ (ACE-$2$) as a receptor to infect human susceptible cells. The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. ACE2 usually converts Angiotensin I in the renin-angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE-$2$, although there are claims that such medications actually reduce lung injury caused by COVID-$19$. We employed bioinformatics and systematic approaches to identify such genetic links, using messenger RNA data peripheral blood cells from COVID-$19$ patients and compared them with blood samples from patients with either chronic heart failure disease or hypertensive diseases. We have also considered the immune response genes with elevated expression in COVID-$19$ to those active in cardiovascular diseases and hypertension. Differentially expressed genes (DEGs) common to COVID-$19$ and chronic heart failure, and common to COVID-$19$ and hypertension, were identified; the involvement of these common genes in the signalling pathways and ontologies studied. COVID-$19$ does not share a large number of differentially expressed genes with the conditions under consideration. However, those that were identified included genes playing roles in T cell functions, toll-like receptor pathways, cytokines, chemokines, cell stress, type 2 diabetes and gastric cancer. We also identified protein-protein interactions, gene regulatory networks and suggested drug and chemical compound interactions using the differentially expressed genes. The result of this study may help in identifying significant targets of treatment that can combat the ongoing pandemic due to SARS-CoV-$2$ infection.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染合并高血压或心血管合并症的个体患严重 2019 年冠状病毒病(COVID-19)的风险增加,死亡率高,但 COVID-19 与心血管疾病的相互作用尚不清楚。因此,我们试图通过鉴定与心血管疾病和高血压发病机制相关的 SARS-CoV-2 感染中表达改变的基因来确定新的相互作用机制。一些最近的研究表明,SARS-CoV-2 使用血管紧张素转换酶-2(ACE-2)作为受体感染人类易感细胞。ACE2 基因在许多人类组织中表达,包括肠道、睾丸、肾脏、心脏和肺。ACE2 通常将肾素-血管紧张素-醛固酮系统中的血管紧张素 I 转化为血管紧张素 II,从而影响血压水平。用于心血管疾病和高血压的 ACE 抑制剂可能会增加 ACE-2 的水平,尽管有人声称这些药物实际上会降低 COVID-19 引起的肺损伤。我们采用生物信息学和系统方法,使用 COVID-19 患者外周血细胞的信使 RNA 数据,并将其与慢性心力衰竭或高血压疾病患者的血液样本进行比较,以鉴定此类遗传联系。我们还考虑了 COVID-19 中表达上调的免疫反应基因与心血管疾病和高血压中活跃的基因。鉴定出 COVID-19 与慢性心力衰竭共有、COVID-19 与高血压共有差异表达基因(DEGs);研究这些共同基因在信号通路和本体论中的参与情况。COVID-19 与所考虑的病症没有大量差异表达基因共享。然而,鉴定出的基因包括在 T 细胞功能、 Toll 样受体途径、细胞因子、趋化因子、细胞应激、2 型糖尿病和胃癌中起作用的基因。我们还使用差异表达基因鉴定了蛋白质-蛋白质相互作用、基因调控网络,并提出了药物和化学化合物相互作用。这项研究的结果可能有助于鉴定出对抗由 SARS-CoV-2 感染引起的持续大流行的重要治疗靶点。