Table_1_Molecular Basis of Cardiac and Vascular Injuries Associated With COVID-19.docx

Background: Coronavirus disease 2019 (COVID-19) is a viral respiratory illness caused by the novel coronavirus SARS-CoV-2. The presence of the pre-existing cardiac disease is associated with an increased likelihood of severe clinical course and mortality in patients with COVID-19. Besides, current evidence indicates that a significant number of patients with COVID-19 also exhibit cardiovascular involvement even in the absence of known cardiac risk factors. Therefore, there is a need to understand the underlying mechanisms and genetic predispositions that explain cardiovascular involvement in COVID-19.Objectives:In silico analysis of publicly available datasets to decipher the molecular basis, potential pathways, and the role of the endothelium in the pathogenesis of cardiac and vascular injuries in COVID-19.Materials and Methods: Consistent significant differentially expressed genes (DEGs) shared by endothelium and peripheral immune cells were identified in five microarray transcriptomic profiling datasets in patients with venous thromboembolism “VTE,” acute coronary syndrome, heart failure and/or cardiogenic shock (main cardiovascular injuries related to COVID-19) compared to healthy controls. The identified genes were further examined in the publicly available transcriptomic dataset for cell/tissue specificity in lung tissue, in different ethnicities and in SARS-CoV-2 infected vs. mock-infected lung tissues and cardiomyocytes.Results: We identified 36 DEGs in blood and endothelium known to play key roles in endothelium and vascular biology, regulation of cellular response to stress as well as endothelial cell migration. Some of these genes were upregulated significantly in SARS-CoV-2 infected lung tissues. On the other hand, some genes with cardioprotective functions were downregulated in SARS-CoV-2 infected cardiomyocytes.Conclusion: In conclusion, our findings from the analysis of publicly available transcriptomic datasets identified shared core genes pertinent to cardiac and vascular-related injuries and their probable role in genetic susceptibility to cardiovascular injury in patients with COVID-19.

背景：新型冠状病毒肺炎（COVID-19）是由新型冠状病毒SARS-CoV-2引起的呼吸道疾病。既往心脏病病史与COVID-19患者严重临床病程和死亡风险增加相关。此外，现有证据表明，大量COVID-19患者即使没有已知的心脏风险因素，也存在心血管受累的情况。因此，有必要理解解释COVID-19中心血管受累的潜在机制和遗传易感性。目标：通过对公开数据集进行计算机模拟分析，揭示COVID-19中心脏和血管损伤的分子基础、潜在通路以及内皮细胞在发病机制中的作用。材料与方法：在比较静脉血栓栓塞（VTE）、急性冠脉综合征、心力衰竭及/或心源性休克（与COVID-19相关的最主要心血管损伤）患者与健康对照者的五组微阵列转录组分析数据集中，确定了内皮细胞和周围免疫细胞共有的显著差异表达基因（DEGs）。这些基因进一步在公开的转录组数据集中进行了检查，以研究其在肺组织、不同民族群体以及SARS-CoV-2感染与模拟感染肺组织和心肌细胞中的细胞/组织特异性。结果：我们鉴定出36个已知在血管生物学、细胞对压力的应激反应调节以及内皮细胞迁移中发挥关键作用的差异表达基因。其中一些基因在SARS-CoV-2感染肺组织中显著上调。另一方面，一些具有心脏保护功能的基因在SARS-CoV-2感染的心肌细胞中下调。结论：综上所述，我们从公开转录组数据集的分析中发现了与心脏和血管相关损伤相关的核心基因，并探讨了它们在COVID-19患者心血管损伤遗传易感性中的可能作用。