| First Author | Li JX | Year | 2024 |
| Journal | Redox Biol | Volume | 69 |
| Pages | 103004 | PubMed ID | 38141575 |
| Mgi Jnum | J:346034 | Mgi Id | MGI:7578434 |
| Doi | 10.1016/j.redox.2023.103004 | Citation | Li JX, et al. (2024) Myeloid ACE2 protects against septic hypotension and vascular dysfunction through Ang-(1-7)-Mas-mediated macrophage polarization. Redox Biol 69:103004 |
| abstractText | 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-kappaB 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. |
