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Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure

Galectin-3 is a biomarker of heart disease. However, it remains unknown whether increase in galectin-3 levels is dependent on aetiology or disease-associated conditions and whether diseased heart releases galectin-3 into the circulation. We explored these questions in mouse models of heart disease a...

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Autores principales: Nguyen, My-Nhan, Su, Yidan, Vizi, Donna, Fang, Lu, Ellims, Andris H., Zhao, Wei-Bo, Kiriazis, Helen, Gao, Xiao-Ming, Sadoshima, Junichi, Taylor, Andrew J., McMullen, Julie R., Dart, Anthony M., Kaye, David M., Du, Xiao-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973942/
https://www.ncbi.nlm.nih.gov/pubmed/29844319
http://dx.doi.org/10.1038/s41598-018-26115-y
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author Nguyen, My-Nhan
Su, Yidan
Vizi, Donna
Fang, Lu
Ellims, Andris H.
Zhao, Wei-Bo
Kiriazis, Helen
Gao, Xiao-Ming
Sadoshima, Junichi
Taylor, Andrew J.
McMullen, Julie R.
Dart, Anthony M.
Kaye, David M.
Du, Xiao-Jun
author_facet Nguyen, My-Nhan
Su, Yidan
Vizi, Donna
Fang, Lu
Ellims, Andris H.
Zhao, Wei-Bo
Kiriazis, Helen
Gao, Xiao-Ming
Sadoshima, Junichi
Taylor, Andrew J.
McMullen, Julie R.
Dart, Anthony M.
Kaye, David M.
Du, Xiao-Jun
author_sort Nguyen, My-Nhan
collection PubMed
description Galectin-3 is a biomarker of heart disease. However, it remains unknown whether increase in galectin-3 levels is dependent on aetiology or disease-associated conditions and whether diseased heart releases galectin-3 into the circulation. We explored these questions in mouse models of heart disease and in patients with cardiomyopathy. All mouse models (dilated cardiomyopathy, DCM; fibrotic cardiomyopathy, ischemia-reperfusion, I/R; treatment with β-adrenergic agonist isoproterenol) showed multi-fold increases in cardiac galectin-3 expression and preserved renal function. In mice with fibrotic cardiomyopathy, I/R or isoproterenol treatment, plasma galectin-3 levels and density of cardiac inflammatory cells were elevated. These models also exhibited parallel changes in cardiac and plasma galectin-3 levels and presence of trans-cardiac galectin-3 gradient, indicating cardiac release of galectin-3. DCM mice showed no change in circulating galectin-3 levels nor trans-cardiac galectin-3 gradient or myocardial inflammatory infiltration despite a 50-fold increase in cardiac galectin-3 content. In patients with hypertrophic cardiomyopathy or DCM, plasma galectin-3 increased only in those with renal dysfunction and a trans-cardiac galectin-3 gradient was not present. Collectively, this study documents the aetiology-dependency and diverse mechanisms of increment in circulating galectin-3 levels. Our findings highlight cardiac inflammation and enhanced β-adrenoceptor activation in mediating elevated galectin-3 levels via cardiac release in the mechanism.
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spelling pubmed-59739422018-05-31 Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure Nguyen, My-Nhan Su, Yidan Vizi, Donna Fang, Lu Ellims, Andris H. Zhao, Wei-Bo Kiriazis, Helen Gao, Xiao-Ming Sadoshima, Junichi Taylor, Andrew J. McMullen, Julie R. Dart, Anthony M. Kaye, David M. Du, Xiao-Jun Sci Rep Article Galectin-3 is a biomarker of heart disease. However, it remains unknown whether increase in galectin-3 levels is dependent on aetiology or disease-associated conditions and whether diseased heart releases galectin-3 into the circulation. We explored these questions in mouse models of heart disease and in patients with cardiomyopathy. All mouse models (dilated cardiomyopathy, DCM; fibrotic cardiomyopathy, ischemia-reperfusion, I/R; treatment with β-adrenergic agonist isoproterenol) showed multi-fold increases in cardiac galectin-3 expression and preserved renal function. In mice with fibrotic cardiomyopathy, I/R or isoproterenol treatment, plasma galectin-3 levels and density of cardiac inflammatory cells were elevated. These models also exhibited parallel changes in cardiac and plasma galectin-3 levels and presence of trans-cardiac galectin-3 gradient, indicating cardiac release of galectin-3. DCM mice showed no change in circulating galectin-3 levels nor trans-cardiac galectin-3 gradient or myocardial inflammatory infiltration despite a 50-fold increase in cardiac galectin-3 content. In patients with hypertrophic cardiomyopathy or DCM, plasma galectin-3 increased only in those with renal dysfunction and a trans-cardiac galectin-3 gradient was not present. Collectively, this study documents the aetiology-dependency and diverse mechanisms of increment in circulating galectin-3 levels. Our findings highlight cardiac inflammation and enhanced β-adrenoceptor activation in mediating elevated galectin-3 levels via cardiac release in the mechanism. Nature Publishing Group UK 2018-05-29 /pmc/articles/PMC5973942/ /pubmed/29844319 http://dx.doi.org/10.1038/s41598-018-26115-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nguyen, My-Nhan
Su, Yidan
Vizi, Donna
Fang, Lu
Ellims, Andris H.
Zhao, Wei-Bo
Kiriazis, Helen
Gao, Xiao-Ming
Sadoshima, Junichi
Taylor, Andrew J.
McMullen, Julie R.
Dart, Anthony M.
Kaye, David M.
Du, Xiao-Jun
Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure
title Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure
title_full Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure
title_fullStr Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure
title_full_unstemmed Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure
title_short Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure
title_sort mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973942/
https://www.ncbi.nlm.nih.gov/pubmed/29844319
http://dx.doi.org/10.1038/s41598-018-26115-y
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