Renin-Angiotensin system and fibrinolytic pathway in COVID-19: One-way skepticism
Renin-Angiotensin system and fibrinolytic pathway in COVID-19: One-way skepticism
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DOI：
10.4103/bbrj.bbrj_105_20
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发表时间：
2020-08-01
影响因子：
1.4
通讯作者：
Lungnier, Claire
中科院分区：
文献类型：
--
作者：
Al-Kuraishy, Hayder;Hussien, Nawar;Lungnier, Claire
严重急性呼吸综合征冠状病毒（SARS-CoV-2）感染是由严重急性呼吸综合征冠状病毒（SARS-CoV-2）引起的近期大流行传染病。SARS-CoV-2的进入点是通过血管紧张素转换酶2 (ACE2)，该酶在肺泡肺细胞中高度表达。此外，不同的多肽和协同介质如慢激肽（BK）、纤溶酶和跨膜丝氨酸蛋白酶可能调节SARS-CoV-2对ACE2的亲和力和结合。因此，本研究计划回顾这些介质对ACE2的调节与SARS-CoV-2感染的发病机制、发病率和严重程度之间的潜在联系。使用MeSH术语、关键词和标题词对Scopus、Web of Science、Medline、Cochrane Central Register of Controlled Trials和PubMed等电子数据库进行检索。肾素-血管紧张素系统抑制剂可能对减少SARS-CoV-2诱导的急性呼吸窘迫综合征（ARDS）、呼吸衰竭和急性肺炎有价值。SARS-CoV-2感染通过下调ACE2导致值得注意的肺损伤，而给予血管紧张素受体阻滞剂（ARBs）可减弱ACE2。在SARS-CoV-2感染中，由于ACE2被SARS-CoV-2下调，BK及其代谢物被增强。SARS-CoV-2肺炎也与高纤维蛋白溶解有关，表现为高循环纤维蛋白降解产物、高纤溶酶和多器官出现出血点。ACEIs通过抑制PAI-1改善纤维蛋白溶解，而arb对纤维蛋白溶解和PAI-1均有中性作用。因此，这些发现表明acei而非ARBs是SARS-CoV-2感染发展的潜在风险，因为纤溶蛋白和BK都促进了SARS-CoV-2的发病机制，并增加了SARS-CoV-2感染中ARDS的发展。
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a recent pandemic infectious disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). The entry point of SARS-CoV-2 is via angiotensin-converting enzyme 2 (ACE2), which is highly expressed in the alveolar pulmonary cells. Besides, different peptides and co-mediators such as bradykinin (BK), plasmin, and trans-membrane serine protease may modulate the affinity and binding of SARS-CoV-2 to ACE2. Therefore, this study was planned to review the potential link between the pathogenesis, incidence, and severity of SARS-CoV-2 infection regarding the modulation of ACE2 by these mediators. Electronic database searches of Scopus, Web of Science, Medline, Cochrane Central Register of Controlled Trials, and PubMed was made using MeSH terms, keywords, and title words. Renin-angiotensin system inhibitors might be of value in the reduction of acute respiratory distress syndrome (ARDS), respiratory failure, and acute pneumonia that are induced by SARS-CoV-2. SARS-CoV-2 infection leads to noteworthy lung injury via downregulation of ACE2, which is attenuated by the administration of angiotensin receptor blockers (ARBs). In SARS-CoV-2 infection, BK and its metabolites are augmented due to the downregulation of ACE2 by SARS-CoV-2. SARS-CoV-2 pneumonia is also associated with hyperfibrinolysis as evident with high circulating fibrin degradation products, high plasmin, and presence of hemorrhagic spots in multiple organs. ACEIs improve fibrinolysis via inhibition of PAI-1, while ARBs have a neutral effect on both fibrinolysis and PAI-1. Therefore, these findings show ACEIs but not ARBs as a potential risk for the development of SARS-CoV-2 infection as both plasmin and BK facilitate the pathogenesis of SARS-CoV-2 and augment the development of ARDS in SARS-CoV-2 infection.