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Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice
BACKGROUND: Macrophages and Wnt proteins (Wnts) are independently involved in cardiac development, response to cardiac injury, and repair. However, the role of macrophage‐derived Wnts in the healing and repair of myocardial infarction (MI) is unknown. We sought to determine the role of macrophage Wn...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523630/ https://www.ncbi.nlm.nih.gov/pubmed/28062479 http://dx.doi.org/10.1161/JAHA.116.004387 |
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author | Palevski, Dahlia Levin‐Kotler, La‐Paz Kain, David Naftali‐Shani, Nili Landa, Natalie Ben‐Mordechai, Tammy Konfino, Tal Holbova, Radka Molotski, Natali Rosin‐Arbesfeld, Rina Lang, Richard A. Leor, Jonathan |
author_facet | Palevski, Dahlia Levin‐Kotler, La‐Paz Kain, David Naftali‐Shani, Nili Landa, Natalie Ben‐Mordechai, Tammy Konfino, Tal Holbova, Radka Molotski, Natali Rosin‐Arbesfeld, Rina Lang, Richard A. Leor, Jonathan |
author_sort | Palevski, Dahlia |
collection | PubMed |
description | BACKGROUND: Macrophages and Wnt proteins (Wnts) are independently involved in cardiac development, response to cardiac injury, and repair. However, the role of macrophage‐derived Wnts in the healing and repair of myocardial infarction (MI) is unknown. We sought to determine the role of macrophage Wnts in infarct repair. METHODS AND RESULTS: We show that the Wnt pathway is activated after MI in mice. Furthermore, we demonstrate that isolated infarct macrophages express distinct Wnt pathway components and are a source of noncanonical Wnts after MI. To determine the effect of macrophage Wnts on cardiac repair, we evaluated mice lacking the essential Wnt transporter Wntless (Wls) in myeloid cells. Significantly, Wntless‐deficient macrophages presented a unique subset of M2‐like macrophages with anti‐inflammatory, reparative, and angiogenic properties. Serial echocardiography studies revealed that mice lacking macrophage Wnt secretion showed improved function and less remodeling 30 days after MI. Finally, mice lacking macrophage‐Wntless had increased vascularization near the infarct site compared with controls. CONCLUSIONS: Macrophage‐derived Wnts are implicated in adverse cardiac remodeling and dysfunction after MI. Together, macrophage Wnts could be a new therapeutic target to improve infarct healing and repair. |
format | Online Article Text |
id | pubmed-5523630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55236302017-08-02 Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice Palevski, Dahlia Levin‐Kotler, La‐Paz Kain, David Naftali‐Shani, Nili Landa, Natalie Ben‐Mordechai, Tammy Konfino, Tal Holbova, Radka Molotski, Natali Rosin‐Arbesfeld, Rina Lang, Richard A. Leor, Jonathan J Am Heart Assoc Original Research BACKGROUND: Macrophages and Wnt proteins (Wnts) are independently involved in cardiac development, response to cardiac injury, and repair. However, the role of macrophage‐derived Wnts in the healing and repair of myocardial infarction (MI) is unknown. We sought to determine the role of macrophage Wnts in infarct repair. METHODS AND RESULTS: We show that the Wnt pathway is activated after MI in mice. Furthermore, we demonstrate that isolated infarct macrophages express distinct Wnt pathway components and are a source of noncanonical Wnts after MI. To determine the effect of macrophage Wnts on cardiac repair, we evaluated mice lacking the essential Wnt transporter Wntless (Wls) in myeloid cells. Significantly, Wntless‐deficient macrophages presented a unique subset of M2‐like macrophages with anti‐inflammatory, reparative, and angiogenic properties. Serial echocardiography studies revealed that mice lacking macrophage Wnt secretion showed improved function and less remodeling 30 days after MI. Finally, mice lacking macrophage‐Wntless had increased vascularization near the infarct site compared with controls. CONCLUSIONS: Macrophage‐derived Wnts are implicated in adverse cardiac remodeling and dysfunction after MI. Together, macrophage Wnts could be a new therapeutic target to improve infarct healing and repair. John Wiley and Sons Inc. 2017-01-06 /pmc/articles/PMC5523630/ /pubmed/28062479 http://dx.doi.org/10.1161/JAHA.116.004387 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://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 | Original Research Palevski, Dahlia Levin‐Kotler, La‐Paz Kain, David Naftali‐Shani, Nili Landa, Natalie Ben‐Mordechai, Tammy Konfino, Tal Holbova, Radka Molotski, Natali Rosin‐Arbesfeld, Rina Lang, Richard A. Leor, Jonathan Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice |
title | Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice |
title_full | Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice |
title_fullStr | Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice |
title_full_unstemmed | Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice |
title_short | Loss of Macrophage Wnt Secretion Improves Remodeling and Function After Myocardial Infarction in Mice |
title_sort | loss of macrophage wnt secretion improves remodeling and function after myocardial infarction in mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523630/ https://www.ncbi.nlm.nih.gov/pubmed/28062479 http://dx.doi.org/10.1161/JAHA.116.004387 |
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