Department of Emergency Medicine, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Worker's Stadium South Road, Beijing, 100020, China.
Department of Emergency Medicine, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Worker's Stadium South Road, Beijing, 100020, China.
Redox Biol. 2024 Feb;69:103004. doi: 10.1016/j.redox.2023.103004. Epub 2023 Dec 18.
Angiotensin converting enzyme 2 (ACE2) is a new identified member of the renin-angiotensin-aldosterone system (RAAS) that cleaves angiotensin II (Ang II) to Ang (1-7), which exerts anti-inflammatory and antioxidative activities via binding with Mas receptor (MasR). However, the functional role of ACE2 in sepsis-related hypotension remains unknown. Our results indicated that sepsis significantly reduced blood pressure and led to disruption between ACE-Ang II and ACE2-Ang (1-7) balance. ACE2 knock-in mice exhibited improved sepsis-induced mortality, hypotension and vascular dysfunction, while ACE2 knockout mice exhibited the opposite effects. Bone marrow transplantation and in vitro experiments confirmed that myeloid ACE2 exerted a protective role by suppressing oxidative stress, NO production and macrophage polarization via the Ang (1-7)-MasR-NF-κB and STAT1 pathways. Thus, ACE2 on myeloid cells could protect against sepsis-mediated hypotension and vascular dysfunction, and upregulating ACE2 may represent a promising therapeutic option for septic patients with hypotension.
血管紧张素转换酶 2（ACE2）是肾素-血管紧张素-醛固酮系统（RAAS）的新成员，可将血管紧张素 II（Ang II）切割为 Ang（1-7），后者通过与 Mas 受体（MasR）结合发挥抗炎和抗氧化作用。然而，ACE2 在与脓毒症相关的低血压中的功能作用仍不清楚。我们的结果表明，脓毒症显著降低血压，并导致 ACE-Ang II 和 ACE2-Ang（1-7）平衡的破坏。ACE2 基因敲入小鼠表现出改善的脓毒症诱导的死亡率、低血压和血管功能障碍，而 ACE2 基因敲除小鼠则表现出相反的效果。骨髓移植和体外实验证实，髓样 ACE2 通过抑制氧化应激、NO 产生和巨噬细胞极化，通过 Ang（1-7）-MasR-NF-κB 和 STAT1 途径发挥保护作用。因此，髓样细胞上的 ACE2 可预防脓毒症引起的低血压和血管功能障碍，上调 ACE2 可能是治疗伴有低血压的脓毒症患者的有前途的选择。
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