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New Role for Interleukin‐13 Receptor α1 in Myocardial Homeostasis and Heart Failure
BACKGROUND: The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins‐4 and ‐13 are anti‐inflammatory type‐2 cytokines, signaling via the common interleukin‐13 receptor α1 chain and the type‐2 interleukin‐4 receptor. The role of interleukin‐13 receptor α1...
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/PMC5524075/ https://www.ncbi.nlm.nih.gov/pubmed/28528324 http://dx.doi.org/10.1161/JAHA.116.005108 |
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author | Amit, Uri Kain, David Wagner, Allon Sahu, Avinash Nevo‐Caspi, Yael Gonen, Nir Molotski, Natali Konfino, Tal Landa, Natalie Naftali‐Shani, Nili Blum, Galia Merquiol, Emmanuelle Karo‐Atar, Danielle Kanfi, Yariv Paret, Gidi Munitz, Ariel Cohen, Haim Y. Ruppin, Eytan Hannenhalli, Sridhar Leor, Jonathan |
author_facet | Amit, Uri Kain, David Wagner, Allon Sahu, Avinash Nevo‐Caspi, Yael Gonen, Nir Molotski, Natali Konfino, Tal Landa, Natalie Naftali‐Shani, Nili Blum, Galia Merquiol, Emmanuelle Karo‐Atar, Danielle Kanfi, Yariv Paret, Gidi Munitz, Ariel Cohen, Haim Y. Ruppin, Eytan Hannenhalli, Sridhar Leor, Jonathan |
author_sort | Amit, Uri |
collection | PubMed |
description | BACKGROUND: The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins‐4 and ‐13 are anti‐inflammatory type‐2 cytokines, signaling via the common interleukin‐13 receptor α1 chain and the type‐2 interleukin‐4 receptor. The role of interleukin‐13 receptor α1 in the heart is unknown. METHODS AND RESULTS: We analyzed myocardial samples from human donors (n=136) and patients with end‐stage heart failure (n=177). We found that the interleukin‐13 receptor α1 is present in the myocardium and, together with the complementary type‐2 interleukin‐4 receptor chain Il4ra, is significantly downregulated in the hearts of patients with heart failure. Next, we showed that Il13ra1‐deficient mice develop severe myocardial dysfunction and dyssynchrony compared to wild‐type mice (left ventricular ejection fraction 29.7±9.9 versus 45.0±8.0; P=0.004, left ventricular end‐diastolic diameter 4.2±0.2 versus 3.92±0.3; P=0.03). A bioinformatic analysis of mouse hearts indicated that interleukin‐13 receptor α1 regulates critical pathways in the heart other than the immune system, such as extracellular matrix (normalized enrichment score=1.90; false discovery rate q=0.005) and glucose metabolism (normalized enrichment score=−2.36; false discovery rate q=0). Deficiency of Il13ra1 was associated with reduced collagen deposition under normal and pressure‐overload conditions. CONCLUSIONS: The results of our studies in humans and mice indicate, for the first time, a role of interleukin‐13 receptor α1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease. |
format | Online Article Text |
id | pubmed-5524075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55240752017-08-02 New Role for Interleukin‐13 Receptor α1 in Myocardial Homeostasis and Heart Failure Amit, Uri Kain, David Wagner, Allon Sahu, Avinash Nevo‐Caspi, Yael Gonen, Nir Molotski, Natali Konfino, Tal Landa, Natalie Naftali‐Shani, Nili Blum, Galia Merquiol, Emmanuelle Karo‐Atar, Danielle Kanfi, Yariv Paret, Gidi Munitz, Ariel Cohen, Haim Y. Ruppin, Eytan Hannenhalli, Sridhar Leor, Jonathan J Am Heart Assoc Original Research BACKGROUND: The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins‐4 and ‐13 are anti‐inflammatory type‐2 cytokines, signaling via the common interleukin‐13 receptor α1 chain and the type‐2 interleukin‐4 receptor. The role of interleukin‐13 receptor α1 in the heart is unknown. METHODS AND RESULTS: We analyzed myocardial samples from human donors (n=136) and patients with end‐stage heart failure (n=177). We found that the interleukin‐13 receptor α1 is present in the myocardium and, together with the complementary type‐2 interleukin‐4 receptor chain Il4ra, is significantly downregulated in the hearts of patients with heart failure. Next, we showed that Il13ra1‐deficient mice develop severe myocardial dysfunction and dyssynchrony compared to wild‐type mice (left ventricular ejection fraction 29.7±9.9 versus 45.0±8.0; P=0.004, left ventricular end‐diastolic diameter 4.2±0.2 versus 3.92±0.3; P=0.03). A bioinformatic analysis of mouse hearts indicated that interleukin‐13 receptor α1 regulates critical pathways in the heart other than the immune system, such as extracellular matrix (normalized enrichment score=1.90; false discovery rate q=0.005) and glucose metabolism (normalized enrichment score=−2.36; false discovery rate q=0). Deficiency of Il13ra1 was associated with reduced collagen deposition under normal and pressure‐overload conditions. CONCLUSIONS: The results of our studies in humans and mice indicate, for the first time, a role of interleukin‐13 receptor α1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease. John Wiley and Sons Inc. 2017-05-20 /pmc/articles/PMC5524075/ /pubmed/28528324 http://dx.doi.org/10.1161/JAHA.116.005108 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Amit, Uri Kain, David Wagner, Allon Sahu, Avinash Nevo‐Caspi, Yael Gonen, Nir Molotski, Natali Konfino, Tal Landa, Natalie Naftali‐Shani, Nili Blum, Galia Merquiol, Emmanuelle Karo‐Atar, Danielle Kanfi, Yariv Paret, Gidi Munitz, Ariel Cohen, Haim Y. Ruppin, Eytan Hannenhalli, Sridhar Leor, Jonathan New Role for Interleukin‐13 Receptor α1 in Myocardial Homeostasis and Heart Failure |
title | New Role for Interleukin‐13 Receptor α1 in Myocardial Homeostasis and Heart Failure |
title_full | New Role for Interleukin‐13 Receptor α1 in Myocardial Homeostasis and Heart Failure |
title_fullStr | New Role for Interleukin‐13 Receptor α1 in Myocardial Homeostasis and Heart Failure |
title_full_unstemmed | New Role for Interleukin‐13 Receptor α1 in Myocardial Homeostasis and Heart Failure |
title_short | New Role for Interleukin‐13 Receptor α1 in Myocardial Homeostasis and Heart Failure |
title_sort | new role for interleukin‐13 receptor α1 in myocardial homeostasis and heart failure |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524075/ https://www.ncbi.nlm.nih.gov/pubmed/28528324 http://dx.doi.org/10.1161/JAHA.116.005108 |
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