Role and mechanism of angiotensin-converting enzyme 2 in acute lung injury in coronavirus disease 2019.
Role and mechanism of angiotensin-converting enzyme 2 in acute lung injury in coronavirus disease 2019.
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DOI：
10.1016/j.cdtm.2020.05.003
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发表时间：
2020-06-01
影响因子：
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通讯作者：
Li, Jian-Ping
中科院分区：
文献类型：
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作者：
Liu, Meng-Yuan;Zheng, Bo;Li, Jian-Ping
2019年冠状病毒病是全球公共卫生的主要威胁。虽然其发病机制尚未完全阐明，但最近已确定血管紧张素转换酶2（ACE 2）是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）进入细胞的受体。本研究旨在阐明ACE 2在SARS-CoV-2诱导的急性肺损伤中的作用及其机制。作为冠状病毒的受体，ACE 2介导SARS-CoV-2进入细胞的方式与严重急性呼吸综合征冠状病毒（SARS-CoV）相似。SARS-CoV-2与ACE 2的高结合亲和力与其在人类中的有效传播相关。另一方面，ACE 2主要通过将血管紧张素II转化为血管紧张素1-7来负性调节肾素-血管紧张素-醛固酮系统（RAAS），这对冠状病毒诱导的急性肺损伤发挥有益作用。人重组ACE 2通过阻断病毒进入细胞，纠正RAAS失衡，被认为是治疗SARS CoV-2的潜在药物。ACE抑制剂（ACEI）或血管紧张素Ⅱ 1型受体阻滞剂（ARB）可上调ACE 2表达水平。迄今为止，没有证据表明ACEI或ARB会增加SARS-CoV-2感染患者的易感性和死亡率，因此，不建议心血管疾病患者停用此类药物。
Coronavirus disease 2019 is a major threat to public health globally. Though its pathogenesis has not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cell. Here, we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism. As a receptor for coronavirus, ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS-CoV). The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans. On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1-7, which exerts a beneficial effect on coronavirus-induced acute lung injury. Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection. The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin Ⅱ type 1 receptor blocker (ARB). To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.