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

Abstract

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.

Reactive Oxygen Species and Strategies for Antioxidant Intervention in Acute Respiratory Distress Syndrome

“…Puncturing the cecum, which contains bacteria, leads to bacterial peritonitis and the translocation of bacteria into the bloodstream, ultimately resulting in septic shock. CLP mice exhibit high mortality and histopathological changes associated with ARDS, including the destruction of the alveolar structure, thickening of the pulmonary septa, hemorrhaged lung tissue, and the infiltration of inflammatory cells [40,41].…”

The rationale of PCSK9 inhibitors in sepsis: a viewpoint

“…Another potential mechanism might BE related to the effect of PCSK9 on angiotensin-converting enzyme 2 (ACE2) entry receptors in COVID-19 [8]. Likewise, it has been reported that ACE2 suppresses abdominal sepsis and severe acute lung injury [9]. It is known that PCSK9 enhances the degradation of ACE2 which is anti-inflammatory by requiring different domains that those critical for the LDL receptor degradation by PCSK9.…”

Research Progress of Macromolecules in the Prevention and Treatment of Sepsis

“…B38-CAP, an ACE2-like enzyme derived from Bacillus-like bacteria, can upregulate the level of angiotensin 1–7, reduce the levels of Ang II and inflammatory cytokines and chemokines, improve lung injury caused by sepsis, and increase the survival rate of CLP mice by 20% [ 48 ].…”