Journal Article

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

Flor, Juliane, Silveira, Andresa Thomé, Martins, Isabel Amaral, Marques da Silva, Laura Tibola, Perin, Fabíola Adelia, Guimarães, Giuliano Rizzotto, Rigatto, Katya, Fagundes, Lucas Sagrillo, Otero, Laura Bastos, Maciel, Lorenzo Santana, Wink, Márcia Rosângela, Eller, Sarah

2025

Overview

Objective: We aimed to assess the expression and localization of renin-angiotensin system (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-min 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 groups, except for 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 bronchiole 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.

• Publisher: MDPI AG
• Subject: Angiotensin AT1 receptors / Angiotensin I / Ethylenediaminetetraacetic acid / G protein-coupled receptors / idiopathic pulmonary fibrosis / Immunohistochemistry / Liquid chromatography / Localization / Lung transplantation / Lung transplants / Mass spectrometry / Mass spectroscopy / Medical research / Medicine, Experimental / Parenchyma / Pathophysiology / Peptides / Plasma levels / Polyclonal antibodies / Protease inhibitors / Proteins / Receptor mechanisms / Renin / renin–angiotensin system / Respiratory function / spirometry / Structure-function relationships