RAS and bradykinin pathways in COVID-19

This pathway describes imbalances in RAS and Bradykinin pathways in COVID-19. The expression of several genes in these pathways is affected in by SARS-CoV-2: * SERPING1 is downregulated, which cancels the suppression of F12 of the intrinsic coagulation cascade, resulting in the production of bradykinin from kallikrein and KNG. * ACE is downregulated, which increases bradykinin levels. * ACE2 is upregulated, ACE is downregulated, which causes an increase in Angiotensin 1-9 and sensitization of bradykinin receptors. * NFkappaB is suppressed by SARS-Cov-2, decreasing its binding to the ACE promoter and subsequent transcription. The result of a hyperactive bradykinin system is vasodilation to the point of vascular leakage and infiltration of inflammatory cells. The pathway is based on figure 2A from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410499/ Garvin et al.]

本路径描述了新型冠状病毒肺炎（COVID-19）中RAS和缓激肽途径的不平衡现象。这些途径中多个基因的表达受到SARS-CoV-2的影响：* SERPING1基因表达下调，导致内源凝血级联反应中的F12抑制被解除，从而由激肽释放酶和KNG产生缓激肽；* ACE基因表达下调，导致缓激肽水平升高；* ACE2基因表达上调，同时ACE基因表达下调，这引起Angiotensin 1-9水平的增加以及缓激肽受体的敏感性增强；* NFkappaB受到SARS-CoV-2的抑制，降低了其与ACE启动子的结合以及后续的转录。过度活跃的缓激肽系统导致血管舒张直至血管渗漏和炎症细胞的浸润。本途径基于文献[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410499/ Garvin et al.]中的图2A。