COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system.
COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system.
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DOI：
10.1038/s41467-021-22713-z
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发表时间：
2021-04-23
影响因子：
16.6
通讯作者：
Lundberg J
中科院分区：
文献类型：
--
作者：
Rysz S;Al-Saadi J;Sjöström A;Farm M;Campoccia Jalde F;Plattén M;Eriksson H;Klein M;Vargas-Paris R;Nyrén S;Abdula G;Ouellette R;Granberg T;Jonsson Fagerlund M;Lundberg J
SARS-CoV-2 使用 ACE2（肾素-血管紧张素-醛固酮系统 (RAAS) 的抑制剂）进入细胞。研究表明 RAAS 失衡会恶化 COVID-19 的预后。我们提出了一个连续的回顾性 COVID-19 队列，其中发现频繁的肺血栓栓塞 (17%)、高肺动脉压 (60%) 和肺 MRI 灌注紊乱。我们在猪身上证明，与对照动物相比，输注血管紧张素 II 或阻断 ACE2 会导致肺动脉压力增加、血液氧合减少、凝血增加、肺灌注扰乱、诱导弥漫性肺泡损伤和急性肾小管坏死。我们进一步证明，这种不平衡状态可以通过输注血管紧张素受体阻滞剂和低分子量肝素来改善。在这项工作中，我们证明了 RAAS 失衡引起的猪的病理生理状态与临床 COVID-19 表现有几个共同特征。因此，我们认为严重的 COVID-19 可能部分是由 RAAS 失衡造成的。 SARS-CoV-2 受体 ACE2 参与肾素-血管紧张素-醛固酮系统 (RAAS)。猪中 RAAS 的过度激活会导致与人类患者中的 COVID-19 相似的疾病状态，这表明 COVID-19 的病理生理学可能至少部分是由该激素系统的失衡驱动的。
SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance. The SARS-CoV-2 receptor ACE2 is involved in the Renin-Angiotensin-Aldosterone System (RAAS). Over-activation of RAAS in swine results in a disease state similar to that of COVID-19 in human patients, suggesting that COVID-19 pathophysiology may be driven, at least in part, by an imbalance of this hormonal system.
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影响因子：
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