Hachim Mahmood Yaseen, Al Heialy Saba, Senok Abiola, Hamid Qutayba, Alsheikh-Ali Alawi
College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, QC, Canada.
Front Cardiovasc Med. 2020 Nov 3;7:582399. doi: 10.3389/fcvm.2020.582399. eCollection 2020.
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. 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. 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. 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. 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.
2019冠状病毒病（COVID-19）是一种由新型冠状病毒SARS-CoV-2引起的病毒性呼吸道疾病。已有心脏病的存在与COVID-19患者出现严重临床病程和死亡的可能性增加相关。此外，目前的证据表明，即使在没有已知心脏危险因素的情况下，大量COVID-19患者也表现出心血管受累。因此，有必要了解解释COVID-19中心血管受累的潜在机制和遗传易感性。通过分析公开可用的数据集来解读COVID-19中心脏和血管损伤发病机制的分子基础、潜在途径以及内皮的作用。在静脉血栓栓塞症（VTE）、急性冠状动脉综合征、心力衰竭和/或心源性休克（与COVID-19相关的主要心血管损伤）患者的五个微阵列转录组分析数据集中，与健康对照相比，鉴定出内皮细胞和外周免疫细胞共有的一致显著差异表达基因（DEG）。在公开可用的转录组数据集中，对鉴定出的基因在肺组织中的细胞/组织特异性、不同种族以及SARS-CoV-2感染与模拟感染的肺组织和心肌细胞中进行了进一步研究。我们在血液和内皮细胞中鉴定出36个DEG，已知它们在内皮细胞和血管生物学、细胞对应激反应的调节以及内皮细胞迁移中起关键作用。其中一些基因在SARS-CoV-2感染的肺组织中显著上调。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。总之，我们对公开可用转录组数据集的分析结果确定了与心脏和血管相关损伤相关的共同核心基因及其在COVID-19患者心血管损伤遗传易感性中的可能作用。
