Oestrogen-mediated upregulation of the Mas receptor contributes to sex differences in acute lung injury and lung vascular barrier regulation

Epidemiological data from the SARS-CoV-2 outbreak suggest sex differences in mortality and vulnerability; however, sex-dependent incidence of acute respiratory distress syndrome (ARDS) remains controversial and the sex-dependent mechanisms of endothelial barrier regulation are unknown. In premenopausal women, increased signalling of angiotensin (Ang)(1–7) via the Mas receptor has been linked to lower cardiovascular risk. Since stimulation of the Ang(1–7)/Mas axis protects the endothelial barrier in acute lung injury (ALI), we hypothesised that increased Ang(1–7)/Mas signalling may protect females over males in ALI/ARDS. Clinical data were collected from Charité inpatients (Berlin) and sex differences in ALI were assessed in wild-type (WT) and Mas-receptor deficient (Mas–/–) mice. Endothelial permeability was assessed as weight change in isolated lungs and as transendothelial electrical resistance (TEER) in vitro. In 734 090 Charité inpatients (2005–2016), ARDS had a higher incidence in men as compared to women. In murine ALI, male WT mice had more lung oedema, protein leaks and histological evidence of injury than female WT mice. Lung weight change in response to platelet-activating factor (PAF) was more pronounced in male WT and female Mas–/– mice than in female WT mice, whereas Mas-receptor expression was higher in female WT lungs. Ovariectomy attenuated protection in female WT mice and reduced Mas-receptor expre...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung biology and experimental studies, Acute lung injury and critical care Original Articles: Acute lung injury and basic science Source Type: research