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Age-related changes in tissue macrophages precede cardiac functional impairment
Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using the Cx(3)cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue mac...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069267/ https://www.ncbi.nlm.nih.gov/pubmed/24861132 |
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author | Pinto, Alexander R. Godwin, James W. Chandran, Anjana Hersey, Lucy Ilinykh, Alexei Debuque, Ryan Wang, Lina Rosenthal, Nadia A. |
author_facet | Pinto, Alexander R. Godwin, James W. Chandran, Anjana Hersey, Lucy Ilinykh, Alexei Debuque, Ryan Wang, Lina Rosenthal, Nadia A. |
author_sort | Pinto, Alexander R. |
collection | PubMed |
description | Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using the Cx(3)cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1(−)GFP(hi) and Mrc1(+)GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1(+)GFP(lo), comprises ~50% of total Mrc1(+) cTMs from 30 weeks of age. Immunostaining and functional assays show that Mrc1(+) cTMs are the principal myeloid sentinels in the mouse heart and that they retain proliferative capacity throughout life. Gene expression profiles of the two Mrc1(+) subsets also reveal that Mrc1(+)GFP(lo) cTMs have a decreased number of immune response genes (Cx(3)cr1, Lpar6, CD9, Cxcr4, Itga6 and Tgfβr1), and an increased number of fibrogenic genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role for cTMs in cardiac fibrosis. These findings identify early age-dependent gene expression changes in cTMs, with significant implications for cardiac tissue injury responses and aging-associated cardiac fibrosis. |
format | Online Article Text |
id | pubmed-4069267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-40692672014-06-25 Age-related changes in tissue macrophages precede cardiac functional impairment Pinto, Alexander R. Godwin, James W. Chandran, Anjana Hersey, Lucy Ilinykh, Alexei Debuque, Ryan Wang, Lina Rosenthal, Nadia A. Aging (Albany NY) Research Paper Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using the Cx(3)cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1(−)GFP(hi) and Mrc1(+)GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1(+)GFP(lo), comprises ~50% of total Mrc1(+) cTMs from 30 weeks of age. Immunostaining and functional assays show that Mrc1(+) cTMs are the principal myeloid sentinels in the mouse heart and that they retain proliferative capacity throughout life. Gene expression profiles of the two Mrc1(+) subsets also reveal that Mrc1(+)GFP(lo) cTMs have a decreased number of immune response genes (Cx(3)cr1, Lpar6, CD9, Cxcr4, Itga6 and Tgfβr1), and an increased number of fibrogenic genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role for cTMs in cardiac fibrosis. These findings identify early age-dependent gene expression changes in cTMs, with significant implications for cardiac tissue injury responses and aging-associated cardiac fibrosis. Impact Journals LLC 2014-05-23 /pmc/articles/PMC4069267/ /pubmed/24861132 Text en Copyright: © 2014 Pinto et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Pinto, Alexander R. Godwin, James W. Chandran, Anjana Hersey, Lucy Ilinykh, Alexei Debuque, Ryan Wang, Lina Rosenthal, Nadia A. Age-related changes in tissue macrophages precede cardiac functional impairment |
title | Age-related changes in tissue macrophages precede cardiac functional impairment |
title_full | Age-related changes in tissue macrophages precede cardiac functional impairment |
title_fullStr | Age-related changes in tissue macrophages precede cardiac functional impairment |
title_full_unstemmed | Age-related changes in tissue macrophages precede cardiac functional impairment |
title_short | Age-related changes in tissue macrophages precede cardiac functional impairment |
title_sort | age-related changes in tissue macrophages precede cardiac functional impairment |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069267/ https://www.ncbi.nlm.nih.gov/pubmed/24861132 |
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