The Glucagon-like peptide-1 (GLP-1) receptor is expressed in the lung having a very important role in the modulation of the Angiotensin Converting Enzymes (ACEs). ACE1 cleaves angiotensin-I into angiotensin-II, which is converted by ACE2 to Ang(1-7). Ang(1-7) has vasodilating effects. The Idiopathic Pulmonary Fibrosis (IPF) is characterized by excessive extracellular matrix deposition disrupting the alveolar architecture and physiology. IPF develops by a sequence of inflammation multifocal process that leads to a fibrotic response. IPF presents pulmonary hypertension and right ventricle hypertrophy.
The aim of this study is to elucidate the effect of precocious treatment with LIR during the inflammatory phase of IPF in ACE1 & ACE2 in the late fibrotic phase in an experimental model of IPF.
IPF was induced in rats by a single intra-tracheal instillation of Bleomycin (BLM, 2.5 mg/kg) on day 0 (D0). From day −1 to day 6, animals were treated with Liraglutide (LIR, 100 μg/kg/12h subcutaneous). On D21 rats were sacrificed. Heart ventricles and lungs were isolated, weighted and frozen. Histology of lungs confirmed interstitial lung fibrosis in all BLM-treated rats.
The real time-PCR levels of ACE-1 & ACE-2 were lower in lungs of BLM-IPF than in controls (40% and 48% reduction, respectively). Right ventricle weight was markedly increased in BLM-IPF rats (+66%). The treatment with LIR at the beginning of the inflammatory phase completely restored the levels ACEs at the fibrotic phase (21D), and prevented the right ventricle hypertrophy.
In conclusion BLM instillation causes local injury with inflammation and alteration of lung vasculature with pulmonary hypertension reflected by right ventricle hypertrophy and related to a reduction in the expression levels of ACEs in the lung, especially ACE2. The precocious LIR treatment in the inflammatory phase prevented all these pathogenic alterations.
20 - 23 May 2017
European Society of Endocrinology