Localization and Expression of Renin-Angiotensin System Re-ceptors in Lung from Transplant Patients: A Case-Control Study

Objective: To assess the expression and localization of RAS receptors in lung tissue and the plasma concentration of related peptides in IPF patients. Materials and Methods: This case-control study involved 19 patients from southern Brazil undergoing lung resection or transplantation. Plasma levels of Angiotensin I, II, A, 1-7, Alamandine were measured via liquid chromatography-tandem mass spectrometry. Lung tissue expression and localization of angiotensin type 1 (AT1), Mas, and Mas-related G-protein-coupled receptor D (MrgD) receptors were evaluated using Western blot and immunohistochemistry. Clinical data and the 6-minute walk test were analyzed to correlate receptor expression with lung function and oxygen dependence. Results: IPF patients showed reduced forced vital capacity (FVC) at 49±13% and forced expiratory volume (FEV1) at 51±14%, with a 60% increase in oxygen dependence. Plasma peptide concentrations were similar between the group, with the exception on Angiotensin I, which was significantly higher in the control group. In IPF lungs, AT1 and Mas receptors were expressed 2.31 and 2.13 times more, respectively, while MrgD expression was lower. Mas receptors were mostly found in alveolar areas, whereas MrgD was predominant in the lung parenchyma. Conclusions: This study indicates that the RAS operates independently within tissue, in addition to its systemic functions, highlighting distinct differences between tissue and plasma RAS activities. The distinct roles of MrgD and Mas receptors in lung structure and function could be pivotal for new therapies, potentially leading to more effective IPF treatments.