ACE2 as therapeutic agent.
ACE2 as therapeutic agent.
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DOI：
10.1042/cs20200570
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发表时间：
2020-10
期刊：
影响因子：
6
通讯作者：
Qiuhong Li;M. Grant;E. Richards;M. Raizada
中科院分区：
文献类型：
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作者：
Qiuhong Li;M. Grant;E. Richards;M. Raizada
血管紧张素转换酶2(ACE2)是肾素-血管紧张素系统(RAS)的重要调节因子，通过调节血管张力、液体和电解质平衡，在心血管内稳中起重要作用。血管紧张素转换酶2作为一种羧基单肽酶，将RAS的关键多肽激素血管紧张素-II(Ang-II)的单一C端残基降解，形成血管紧张素-(1-7)(Ang-(1-7))，与G蛋白偶联的Mas受体结合，激活信号通路，抵消Ang-II激活的信号通路。ACE2在多种组织中表达，在实验模型中，大量证据证明在这些组织的许多病理条件下增强ACE2/Ang-(1-7)/mas轴的有益效果。这篇综述将简要概述目前加强ACE2作为治疗剂的策略，并讨论限制和未来的挑战。ACE2还具有其他功能，如作为氨基酸转运的辅助因子和被严重急性呼吸综合征冠状病毒(SARS-CoV)利用作为细胞进入受体，这些功能在基于ACE2的疗法的发展中的意义也将被讨论。
The angiotensin-converting enzyme 2 (ACE2) has emerged as a critical regulator of the renin-angiotensin system (RAS), which plays important roles in cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance. ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein-coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2/Ang-(1-7)/Mas axis under many pathological conditions in these tissues in experimental models. This review will provide a succinct overview on current strategies to enhance ACE2 as therapeutic agent, and discuss limitations and future challenges. ACE2 also has other functions, such as acting as a co-factor for amino acid transport and being exploited by the severe acute respiratory syndrome coronaviruses (SARS-CoVs) as cellular entry receptor, the implications of these functions in development of ACE2-based therapeutics will also be discussed.