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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Format: | Article |
Language: | English |
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Wiley
2023-01-01
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Series: | Pulmonary Circulation |
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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. |
first_indexed | 2024-03-13T10:34:43Z |
format | Article |
id | doaj.art-16a25bb0bb6246239623642815574591 |
institution | Directory Open Access Journal |
issn | 2045-8940 |
language | English |
last_indexed | 2024-03-13T10:34:43Z |
publishDate | 2023-01-01 |
publisher | Wiley |
record_format | Article |
series | Pulmonary Circulation |
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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