COVID-19 相关的血管内皮功能障碍和微血管损伤：从病理生理学到临床表现。
COVID-19-Associated Endothelial Dysfunction and Microvascular Injury: From Pathophysiology to Clinical Manifestations.
机构信息
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
出版信息
Card Electrophysiol Clin. 2022 Mar;14(1):21-28. doi: 10.1016/j.ccep.2021.10.003. Epub 2021 Oct 30.
Abstract
Coronavirus-19 disease (COVID-19) affects more people than previous coronavirus infections and has a higher mortality. Higher incidence and mortality can probably be explained by COVID-19 causative agent's greater affinity (about 10-20 times) for angiotensin-converting enzyme 2 (ACE2) receptor compared with other coronaviruses. Here, the authors first summarize clinical manifestations, then present symptoms of COVID-19 and the pathophysiological mechanisms underlying specific organ/system disease. The worse clinical outcome observed in COVID-19 patients with diabetes may be in part related to the increased ADAM17 activity and its unbalanced interplay with ACE2. Therefore, strategies aimed to inhibit ADAM17 activity may be explored to develop new effective therapeutic approaches.
摘要
新型冠状病毒病（COVID-19）比以往的冠状病毒感染影响更多的人，且死亡率更高。COVID-19 病原体对血管紧张素转换酶 2（ACE2）受体的亲和力（约 10-20 倍）高于其他冠状病毒，可能可以解释其更高的发病率和死亡率。在这里，作者首先总结了临床表现，然后介绍了 COVID-19 的症状以及特定器官/系统疾病的病理生理机制。在 COVID-19 合并糖尿病患者中观察到的更差的临床结局，可能部分与 ADAM17 活性增加及其与 ACE2 的不平衡相互作用有关。因此，可能需要探索旨在抑制 ADAM17 活性的策略，以开发新的有效治疗方法。
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2
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