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The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension
Right ventricular (RV) failure is the primary cause of death in pulmonary hypertension (PH), but the mechanisms of RV failure are not well understood. We hypothesized macrophages in the RV contribute to the RV response in PH. We induced PH in mice with hypoxia (FiO(2) 10%) and Schistosoma mansoni ex...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297026/ https://www.ncbi.nlm.nih.gov/pubmed/35874852 http://dx.doi.org/10.1002/pul2.12105 |
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author | Gu, Sue Mickael, Claudia Kumar, Rahul Lee, Michael H. Sanders, Linda Kassa, Biruk Harral, Julie Williams, Jason Hansen, Kirk C. Stenmark, Kurt R. Tuder, Rubin M. Graham, Brian B. |
author_facet | Gu, Sue Mickael, Claudia Kumar, Rahul Lee, Michael H. Sanders, Linda Kassa, Biruk Harral, Julie Williams, Jason Hansen, Kirk C. Stenmark, Kurt R. Tuder, Rubin M. Graham, Brian B. |
author_sort | Gu, Sue |
collection | PubMed |
description | Right ventricular (RV) failure is the primary cause of death in pulmonary hypertension (PH), but the mechanisms of RV failure are not well understood. We hypothesized macrophages in the RV contribute to the RV response in PH. We induced PH in mice with hypoxia (FiO(2) 10%) and Schistosoma mansoni exposure, and in rats with SU5416‐hypoxia. We quantified cardiac macrophages in mice using flow cytometry. Parabiosis between congenic CD45.1/.2 mice or Cx3cr1‐green fluorescent protein and wild‐type mice was used to quantify circulation‐derived macrophages in experimental PH conditions. We administered clodronate liposomes to Sugen hypoxia (SU‐Hx) exposed rats to deplete macrophages and evaluated the effect on the extracellular matrix (ECM) and capillary network in the RV. In hypoxia exposed mice, the overall number of macrophages did not significantly change but two macrophage subpopulations increased. Parabiosis identified populations of RV macrophages that at steady state is derived from the circulation, with one subpopulation that significantly increased with PH stimuli. Clodronate treatment of SU‐Hx rats resulted in a change in the RV ECM, without altering the RV vasculature, and correlated with improved RV function. Populations of RV macrophages increase and contribute to RV remodeling in PH, including through regulation of the RV ECM. |
format | Online Article Text |
id | pubmed-9297026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92970262022-07-22 The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension Gu, Sue Mickael, Claudia Kumar, Rahul Lee, Michael H. Sanders, Linda Kassa, Biruk Harral, Julie Williams, Jason Hansen, Kirk C. Stenmark, Kurt R. Tuder, Rubin M. Graham, Brian B. Pulm Circ Research Articles Right ventricular (RV) failure is the primary cause of death in pulmonary hypertension (PH), but the mechanisms of RV failure are not well understood. We hypothesized macrophages in the RV contribute to the RV response in PH. We induced PH in mice with hypoxia (FiO(2) 10%) and Schistosoma mansoni exposure, and in rats with SU5416‐hypoxia. We quantified cardiac macrophages in mice using flow cytometry. Parabiosis between congenic CD45.1/.2 mice or Cx3cr1‐green fluorescent protein and wild‐type mice was used to quantify circulation‐derived macrophages in experimental PH conditions. We administered clodronate liposomes to Sugen hypoxia (SU‐Hx) exposed rats to deplete macrophages and evaluated the effect on the extracellular matrix (ECM) and capillary network in the RV. In hypoxia exposed mice, the overall number of macrophages did not significantly change but two macrophage subpopulations increased. Parabiosis identified populations of RV macrophages that at steady state is derived from the circulation, with one subpopulation that significantly increased with PH stimuli. Clodronate treatment of SU‐Hx rats resulted in a change in the RV ECM, without altering the RV vasculature, and correlated with improved RV function. Populations of RV macrophages increase and contribute to RV remodeling in PH, including through regulation of the RV ECM. John Wiley and Sons Inc. 2022-07-01 /pmc/articles/PMC9297026/ /pubmed/35874852 http://dx.doi.org/10.1002/pul2.12105 Text en © 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Gu, Sue Mickael, Claudia Kumar, Rahul Lee, Michael H. Sanders, Linda Kassa, Biruk Harral, Julie Williams, Jason Hansen, Kirk C. Stenmark, Kurt R. Tuder, Rubin M. Graham, Brian B. The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension |
title | The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension |
title_full | The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension |
title_fullStr | The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension |
title_full_unstemmed | The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension |
title_short | The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension |
title_sort | role of macrophages in right ventricular remodeling in experimental pulmonary hypertension |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297026/ https://www.ncbi.nlm.nih.gov/pubmed/35874852 http://dx.doi.org/10.1002/pul2.12105 |
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