ACE2-like enzyme B38-CAP suppresses abdominal sepsis and severe acute lung injury.
Takafumi MinatoTomokazu YamaguchiMidori HoshizakiSatoru NirasawaJianbo AnSaori TakahashiJosef M PenningerYumiko ImaiKeiji KubaPublished in: PloS one (2022)
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.
Keyphrases
- angiotensin ii
- angiotensin converting enzyme
- acute respiratory distress syndrome
- vascular smooth muscle cells
- lipopolysaccharide induced
- septic shock
- intensive care unit
- acute kidney injury
- lps induced
- high glucose
- endothelial cells
- extracorporeal membrane oxygenation
- mechanical ventilation
- high fat diet induced
- sars cov
- heart failure
- cardiovascular disease
- drug induced
- diabetic rats
- poor prognosis
- oxidative stress
- inflammatory response
- blood pressure
- signaling pathway
- early onset
- escherichia coli
- metabolic syndrome
- atrial fibrillation
- wild type
- coronary artery disease
- skeletal muscle
- binding protein
- pluripotent stem cells
- left ventricular
- free survival