Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
Nat Commun. 2021 Apr 23;12(1):2417. doi: 10.1038/s41467-021-22713-z.
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.
SARS-CoV-2 使用 ACE2，即肾素-血管紧张素-醛固酮系统（RAAS）的抑制剂，实现细胞进入。研究表明，RAAS 失衡会使 COVID-19 的预后恶化。我们报告了一项连续的 COVID-19 回顾性队列研究结果，发现频繁发生肺血栓栓塞症（17%）、肺动脉高压（60%）和肺部 MRI 灌注障碍。我们在猪模型中证明，与对照组动物相比，输注血管紧张素 II 或阻断 ACE2 会导致肺动脉压升高、血氧降低、凝血增加、肺灌注紊乱、弥漫性肺泡损伤和急性肾小管坏死。我们进一步证明，这种失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得到改善。在这项工作中，我们表明，由 RAAS 失衡引起的猪的病理生理状态与 COVID-19 的临床特征有一些相似之处。因此，我们提出严重的 COVID-19 可能部分是由 RAAS 失衡引起的。
