Department of Emergency Medicine, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Worker's Stadium South Roud, Beijing, 100020, China.
Cell Biol Toxicol. 2024 Sep 25;40(1):82. doi: 10.1007/s10565-024-09923-z.
Angiotensin-converting enzyme 2 (ACE2), a crucial element of the renin-angiotensin system (RAS), metabolizes angiotensin II into Ang (1-7), which then combines with the Mas receptor (MasR) to fulfill its protective role in various diseases. Nevertheless, the involvement of ACE2 in sepsis-induced cardiomyopathy (SIC) is still unexplored. In this study, our results revealed that CLP surgery dramatically impaired cardiac function accompanied with disruption of the balance between ACE2-Ang (1-7) and ACE-Ang II axis in septic heart tissues. Moreover, ACE2 knockin markedly alleviated sepsis induced RAS disorder, cardiac dysfunction and improved survival rate in mice, while ACE2 knockout significantly exacerbates these outcomes. Adoptive transfer of bone marrow cells and in vitro experiments showed the positive role of myeloid ACE2 by mitigating oxidative stress, inflammatory response, macrophage polarization and cardiomyocyte apoptosis by blocking NF-κB and STAT1 signals. However, the beneficial impacts were nullified by MasR antagonist A779. Collectively, these findings showed that ACE2 alleviated SIC by inhibiting M1 macrophage via activating the Ang (1-7)-MasR axis, highlight that ACE2 might be a promising target for the management of sepsis and SIC patients.
血管紧张素转换酶 2（ACE2）是肾素-血管紧张素系统（RAS）的重要组成部分，可将血管紧张素 II 代谢为 Ang（1-7），然后与 Mas 受体（MasR）结合，在各种疾病中发挥其保护作用。然而，ACE2 在脓毒症性心肌病（SIC）中的作用尚不清楚。在本研究中，我们的结果表明，CLP 手术可显著损害心功能，同时破坏脓毒症心脏组织中 ACE2-Ang（1-7）和 ACE-Ang II 轴之间的平衡。此外，ACE2 基因敲入可显著减轻脓毒症诱导的 RAS 紊乱、心功能障碍，并提高小鼠的存活率，而 ACE2 基因敲除则显著加重这些结果。骨髓细胞的过继转移和体外实验表明，髓样 ACE2 通过阻断 NF-κB 和 STAT1 信号，减轻氧化应激、炎症反应、巨噬细胞极化和心肌细胞凋亡，发挥积极作用。然而，MasR 拮抗剂 A779 可使这些有益作用失效。综上所述，这些发现表明 ACE2 通过激活 Ang（1-7）-MasR 轴抑制 M1 巨噬细胞从而减轻 SIC，提示 ACE2 可能成为脓毒症和 SIC 患者治疗的有希望的靶点。
Zotero 插件
