The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin–angiotensin system (RAS) in favor of the ACE–angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II–AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.

中文翻译：

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血管紧张素 II I 型受体 (AT1R)：通往 COVID-19 相关疾病的大门

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 刺突糖蛋白与其细胞受体血管紧张素转换酶 2 (ACE2) 的结合导致其下调，随后导致肾素-血管紧张素系统失调(RAS) 支持 ACE-血管紧张素 II (Ang II)-血管紧张素 II I 型受体 (AT1R) 轴。AT1R 通过参与多种生理事件（包括血压控制和电解质平衡）在 RAS 中发挥重要作用。SARS-CoV-2 感染后，Ang II-AT1R 轴激活的血管收缩、促炎、促纤维化和促氧化后果产生的致病性发作伴随着过度炎症状态（细胞因子风暴）和急性呼吸窘迫综合征 (ARDS)。AT1R, G 蛋白偶联受体 (GPCR) 家族的一员，通过激活多个下游信号通路调节 Ang II 的有害作用，其中包括 MAP 激酶（ERK 1/2、JNK、p38MAPK）、受体酪氨酸激酶（PDGF、 EGFR，胰岛素受体）和非受体酪氨酸激酶（Src、JAK/STAT、粘着斑激酶 (FAK)）和烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶。众所周知，COVID-19 会产生呼吸道症状，但由于 ACE2 在各种身体组织中均有表达，因此还会出现多种肺外病变，包括神经系统疾病、血管系统和心肌并发症、肾损伤、胃肠道症状、肝损伤、高血糖和皮肤病并发症。因此，以RAS阻滞剂为基础的药物开发，例如抑制 RAS 级联损伤轴的血管紧张素 II 受体阻滞剂 (ARB) 可能在不久的将来成为治疗 COVID-19 最有希望的方法之一。我们在此回顾了 AT1R 的一般特征，特别关注受体介导的不同下游信号通路的激活，从而导致特定的细胞反应。此外，我们提供了关于 AT1R 在人体不同系统中 COVID-19 结果中的作用的最新见解，以及 ARB 作为治疗 COVID-19 的试验性药物的作用。特别关注受体介导的不同下游信号通路的激活，从而导致特定的细胞反应。此外，我们提供了关于 AT1R 在人体不同系统中 COVID-19 结果中的作用的最新见解，以及 ARB 作为治疗 COVID-19 的试验性药物的作用。特别关注受体介导的不同下游信号通路的激活，从而导致特定的细胞反应。此外，我们提供了关于 AT1R 在人体不同系统中 COVID-19 结果中的作用的最新见解，以及 ARB 作为治疗 COVID-19 的试验性药物的作用。