The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Pathophysiology and Clinical Implications.
The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Pathophysiology and Clinical Implications.
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重症COVID-19患者肺肾素-血管紧张素系统的反调控轴：病理生理学和临床意义
DOI：
10.1016/j.hlc.2020.11.008
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Boudoulas H
中科院分区：
文献类型：
--
作者：
Triposkiadis F;Starling RC;Xanthopoulos A;Butler J;Boudoulas H
严重急性呼吸综合征冠状病毒（SARS-CoV）-2是导致2019冠状病毒病（COVID-19）的原因，它使用血管紧张素（ANG）转换酶2（ACE 2）作为入口受体。虽然大多数COVID-19病例是轻度的，但有些是严重或危重的，主要是由于急性肺损伤。已被广泛接受的是，包括ACE 2/ANG [1-7]/Mas在内的反调节性肾素-血管紧张素系统（RAS）轴可保护肺免受急性肺损伤。然而，最近的证据表明，肺中保护性ANG [1-7]的产生主要由促炎性脯氨酰寡肽酶（POP）介导，其已被反复证明参与肺病理学。该综述认为，严重COVID-19的急性肺损伤的特征是a）ACE 2下调和功能障碍（炎症信号传导），和B）保护性RAS轴的失调，主要是由于促炎性POP活性增加。因此，COVID-19相关急性肺损伤的合理治疗策略将是递送功能性重组（r）ACE 2形成以捕获病毒。此外，或替代rACE 2的交付，降低持久性有机污染物的活动所带来的潜在好处也应该探讨。这些治疗策略值得进一步研究。
The severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which is responsible for coronavirus disease 2019 (COVID-19), uses angiotensin (ANG)-converting enzyme 2 (ACE2) as the entrance receptor. Although most COVID-19 cases are mild, some are severe or critical, predominantly due to acute lung injury. It has been widely accepted that a counter regulatory renin-angiotensin system (RAS) axis including the ACE2/ANG [1-7]/Mas protects the lungs from acute lung injury. However, recent evidence suggests that the generation of protective ANG [1-7] in the lungs is predominantly mediated by proinflammatory prolyl oligopeptidase (POP), which has been repeatedly demonstrated to be involved in lung pathology. This review contends that acute lung injury in severe COVID-19 is characterised by a) ACE2 downregulation and malfunction (inflammatory signalling) due to viral occupation, and b) dysregulation of the protective RAS axis, predominantly due to increased activity of proinflammatory POP. It follows that a reasonable treatment strategy in COVID-19-related acute lung injury would be delivering functional recombinant (r) ACE2 forms to trap the virus. Additionally, or alternatively to rACE2 delivery, the potential benefits resulting from lowering POP activity should also be explored. These treatment strategies deserve further investigation.
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