Bleomycin‐induced lung injury: Revisiting an old tool to model group III PH associated with pulmonary fibrosis

Abstract Pulmonary hypertension (PH) is a chronic disorder of the pulmonary circulation that often associates with other respiratory diseases (i.e., group III PH), leading to worsened symptoms and prognosis, notably when combined with interstitial lung diseases such as pulmonary fibrosis (PF). PH ma...

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Main Authors: Diana Santos‐Ribeiro, Marylène Lecocq, Michele deBeukelaer, Caroline Bouzin, Mihaly Palmai‐Pallag, Yousef Yakoub, François Huaux, Sandrine Horman, Frederic Perros, Charles Pilette, Laurent Godinas
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Pulmonary Circulation
Subjects:
Online Access:https://doi.org/10.1002/pul2.12177
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author Diana Santos‐Ribeiro
Marylène Lecocq
Michele deBeukelaer
Caroline Bouzin
Mihaly Palmai‐Pallag
Yousef Yakoub
François Huaux
Sandrine Horman
Frederic Perros
Charles Pilette
Laurent Godinas
author_facet Diana Santos‐Ribeiro
Marylène Lecocq
Michele deBeukelaer
Caroline Bouzin
Mihaly Palmai‐Pallag
Yousef Yakoub
François Huaux
Sandrine Horman
Frederic Perros
Charles Pilette
Laurent Godinas
author_sort Diana Santos‐Ribeiro
collection DOAJ
description Abstract Pulmonary hypertension (PH) is a chronic disorder of the pulmonary circulation that often associates with other respiratory diseases (i.e., group III PH), leading to worsened symptoms and prognosis, notably when combined with interstitial lung diseases such as pulmonary fibrosis (PF). PH may lead to right ventricular (RV) failure, which accounts for a substantial part of the mortality in chronic lung disease patients. The disappointing results of pulmonary arterial hypertension (PAH)‐related therapies in patients with PF emphasize the need to better understand the pathophysiologic mechanisms that drive PH development and progression in this specific setting. In this work, we validated an animal model of group III PH associated with PF (PH‐PF), by using bleomycin (BM) intratracheal instillation and characterizing the nature of induced lung and vascular remodeling, including the influence on RV structure and function. To our knowledge, this is the first work describing this dose of BM in Sprague Dawley rats and the effects upon the heart and lungs, using different techniques such as echocardiography, heart catheterization, and histology. Our data shows the successful implementation of a rat model that mimics combined PF‐PH, with most features seen in the equivalent human disease, such as lung and arterial remodeling, increased mPAP and RV dysfunction.
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spelling doaj.art-16a25bb0bb62462396236428155745912023-05-18T06:26:29ZengWileyPulmonary Circulation2045-89402023-01-01131n/an/a10.1002/pul2.12177Bleomycin‐induced lung injury: Revisiting an old tool to model group III PH associated with pulmonary fibrosisDiana Santos‐Ribeiro0Marylène Lecocq1Michele deBeukelaer2Caroline Bouzin3Mihaly Palmai‐Pallag4Yousef Yakoub5François Huaux6Sandrine Horman7Frederic Perros8Charles Pilette9Laurent Godinas10Pneumology, ENT and Dermatology, Institute of Experimental and Clinical Research (IREC) Université catholique de Louvain (UCL) Brussels BelgiumPneumology, ENT and Dermatology, Institute of Experimental and Clinical Research (IREC) Université catholique de Louvain (UCL) Brussels BelgiumImaging Platform (2IP), Institute of Experimental and Clinical Research (IREC) Université catholique de Louvain (UCL) Brussels BelgiumImaging Platform (2IP), Institute of Experimental and Clinical Research (IREC) Université catholique de Louvain (UCL) Brussels BelgiumInstitute of Experimental and Clinical Research (IREC), Louvain Center for Toxicology and Applied Pharmacology Université catholique de Louvain (UCL) Brussels BelgiumInstitute of Experimental and Clinical Research (IREC), Louvain Center for Toxicology and Applied Pharmacology Université catholique de Louvain (UCL) Brussels BelgiumInstitute of Experimental and Clinical Research (IREC), Louvain Center for Toxicology and Applied Pharmacology Université catholique de Louvain (UCL) Brussels BelgiumInstitute of Experimental and Clinical Research (IREC), Cardiovascular Research Unit Université catholique de Louvain (UCL) Brussels BelgiumLaboratoire CarMeN, UMR INSERM U1060/INRA U1397 Université Claude Bernard Lyon1 Pierre‐Bénite and Bron FrancePneumology, ENT and Dermatology, Institute of Experimental and Clinical Research (IREC) Université catholique de Louvain (UCL) Brussels BelgiumClinical Department of Respiratory Diseases, University Hospitals and Laboratory of Respiratory Diseases & ThoracicSurgery (BREATHE), Department of Chronic Diseases & Metabolism (CHROMETA) KU Leuven—University of Leuven Leuven BelgiumAbstract Pulmonary hypertension (PH) is a chronic disorder of the pulmonary circulation that often associates with other respiratory diseases (i.e., group III PH), leading to worsened symptoms and prognosis, notably when combined with interstitial lung diseases such as pulmonary fibrosis (PF). PH may lead to right ventricular (RV) failure, which accounts for a substantial part of the mortality in chronic lung disease patients. The disappointing results of pulmonary arterial hypertension (PAH)‐related therapies in patients with PF emphasize the need to better understand the pathophysiologic mechanisms that drive PH development and progression in this specific setting. In this work, we validated an animal model of group III PH associated with PF (PH‐PF), by using bleomycin (BM) intratracheal instillation and characterizing the nature of induced lung and vascular remodeling, including the influence on RV structure and function. To our knowledge, this is the first work describing this dose of BM in Sprague Dawley rats and the effects upon the heart and lungs, using different techniques such as echocardiography, heart catheterization, and histology. Our data shows the successful implementation of a rat model that mimics combined PF‐PH, with most features seen in the equivalent human disease, such as lung and arterial remodeling, increased mPAP and RV dysfunction.https://doi.org/10.1002/pul2.12177animal modelcardiovascular diseaseslung remodeling and fibrosis
spellingShingle Diana Santos‐Ribeiro
Marylène Lecocq
Michele deBeukelaer
Caroline Bouzin
Mihaly Palmai‐Pallag
Yousef Yakoub
François Huaux
Sandrine Horman
Frederic Perros
Charles Pilette
Laurent Godinas
Bleomycin‐induced lung injury: Revisiting an old tool to model group III PH associated with pulmonary fibrosis
Pulmonary Circulation
animal model
cardiovascular diseases
lung remodeling and fibrosis
title Bleomycin‐induced lung injury: Revisiting an old tool to model group III PH associated with pulmonary fibrosis
title_full Bleomycin‐induced lung injury: Revisiting an old tool to model group III PH associated with pulmonary fibrosis
title_fullStr Bleomycin‐induced lung injury: Revisiting an old tool to model group III PH associated with pulmonary fibrosis
title_full_unstemmed Bleomycin‐induced lung injury: Revisiting an old tool to model group III PH associated with pulmonary fibrosis
title_short Bleomycin‐induced lung injury: Revisiting an old tool to model group III PH associated with pulmonary fibrosis
title_sort bleomycin induced lung injury revisiting an old tool to model group iii ph associated with pulmonary fibrosis
topic animal model
cardiovascular diseases
lung remodeling and fibrosis
url https://doi.org/10.1002/pul2.12177
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