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- Title
ACE2 Expressed on Myeloid Cells Alleviates Sepsis-Induced Acute Liver Injury via the Ang-(1–7)–Mas Receptor Axis.
- Authors
Liu, Lei; Li, Ya; Li, Jia-Xin; Xiao, Xue; Wan, Tian-Tian; Li, Hui-Hua; Guo, Shu-Bin
- Abstract
Sepsis-induced acute liver injury (ALI) is common in intensive care units. Angiotensin-converting enzyme 2 (ACE2) plays a vital role in hepatic fibrosis and steatosis; however, its role in sepsis-induced ALI remains unclear. This study found that hepatic ACE2 expression in cecal ligation and puncture (CLP)-treated mice significantly decreased 24 h after CLP. ACE2-transgenic (TG) mice exhibited a significant improvement in CLP-induced ALI, accompanied by the inhibition of hepatocyte apoptosis, oxidative stress, and inflammation, while ACE2-knockout mice demonstrated an opposite trend. During sepsis-induced ALI, ACE2-TG could also elevate the Ang-(1–7) and Mas receptor (MasR) levels in liver tissues. Interestingly, the MasR inhibitor A779 abrogated the favorable effects of ACE2 on CLP-induced ALI. In a bone marrow transplantation experiment, the ACE2-TG transplantation group showed significantly improved inflammation and liver dysfunction, less hepatocyte apoptosis, and reduced oxidative stress after CLP compared with the wild-type transplantation group. In contrast, the ACE2-knockout group showed poor inflammatory response and liver dysfunction, significantly more hepatocyte apoptosis, and elevated oxidative stress than the wild-type transplantation group after CLP. ACE2 protects against sepsis-induced ALI by inhibiting hepatocyte apoptosis, oxidative stress, and inflammation via the Ang-(1–7)–Mas receptor axis. Thus, targeting ACE2 may be a promising novel strategy for preventing and treating sepsis-induced ALI.
- Subjects
CAIRO (Egypt); MYELOID cells; ANGIOTENSIN converting enzyme; LIVER injuries; BONE marrow transplantation; APOPTOSIS inhibition
- Publication
Inflammation, 2024, Vol 47, Issue 3, p891
- ISSN
0360-3997
- Publication type
Article
- DOI
10.1007/s10753-023-01949-5