ACE2-like enzyme B38-CAP suppresses abdominal sepsis and severe acute lung injury

Takafumi Minato, Tomokazu Yamaguchi, Midori Hoshizaki, Satoru Nirasawa, Jianbo An, Saori Takahashi, Josef M. Penninger, Yumiko Imai, Keiji Kuba

研究成果: ジャーナルへの寄稿学術誌査読


Angiotensin-converting enzyme 2 (ACE2) is the carboxypeptidase to degrade angiotensin II (Ang II) to angiotensin 1–7 (Ang 1–7) and improves the pathologies of cardiovascular disease and acute respiratory distress syndrome (ARDS)/acute lung injury. B38-CAP is a bacteria-derived ACE2-like carboxypeptidase as potent as human ACE2 and ameliorates hypertension, heart failure and SARS-CoV-2-induced lung injury in mice. Recombinant B38-CAP is prepared with E. coli protein expression system more efficiently than recombinant soluble human ACE2. Here we show therapeutic effects of B38-CAP on abdominal sepsis- or acid aspiration-induced acute lung injury. ACE2 expression was downregulated in the lungs of mice with cecal ligation puncture (CLP)-induced sepsis or acid-induced lung injury thereby leading to upregulation of Ang II levels. Intraperitoneal injection of B38-CAP significantly decreased Ang II levels while upregulated angiotensin 1–7 levels. B38-CAP improved survival rate of the mice under sepsis. B38-CAP suppressed the pathologies of lung inflammation, improved lung dysfunction and downregulated elevated cytokine mRNA levels in the mice with acute lung injury. Thus, systemic treatment with an ACE2-like enzyme might be a potential therapeutic strategy for the patients with severe sepsis or ARDS.

ジャーナルPloS one
7 July
出版ステータス出版済み - 7月 2022

!!!All Science Journal Classification (ASJC) codes

  • 一般


「ACE2-like enzyme B38-CAP suppresses abdominal sepsis and severe acute lung injury」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。