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The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study

INTRODUCTION: Increased galectin-3 is associated with ischemic cardiomyopathy, although its role in early remodeling post-myocardial infarction (MI) has not been fully elucidated. There are no data demonstrating that blocking galectin-3 expression would have an impact on the heart and that its relat...

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Autores principales: Mosleh, Wassim, Chaudhari, Milind R, Sonkawade, Swati, Mahajan, Supriya, Khalil, Charl, Frodey, Kevin, Shah, Tanvi, Dahal, Suraj, Karki, Roshan, Katkar, Rujuta, Blankesteijn, W Matthijs, Page, Brian, Pokharel, Saraswati, Kim, Minhyung, Sharma, Umesh C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946633/
https://www.ncbi.nlm.nih.gov/pubmed/29769800
http://dx.doi.org/10.1177/1177271918771969
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author Mosleh, Wassim
Chaudhari, Milind R
Sonkawade, Swati
Mahajan, Supriya
Khalil, Charl
Frodey, Kevin
Shah, Tanvi
Dahal, Suraj
Karki, Roshan
Katkar, Rujuta
Blankesteijn, W Matthijs
Page, Brian
Pokharel, Saraswati
Kim, Minhyung
Sharma, Umesh C
author_facet Mosleh, Wassim
Chaudhari, Milind R
Sonkawade, Swati
Mahajan, Supriya
Khalil, Charl
Frodey, Kevin
Shah, Tanvi
Dahal, Suraj
Karki, Roshan
Katkar, Rujuta
Blankesteijn, W Matthijs
Page, Brian
Pokharel, Saraswati
Kim, Minhyung
Sharma, Umesh C
author_sort Mosleh, Wassim
collection PubMed
description INTRODUCTION: Increased galectin-3 is associated with ischemic cardiomyopathy, although its role in early remodeling post-myocardial infarction (MI) has not been fully elucidated. There are no data demonstrating that blocking galectin-3 expression would have an impact on the heart and that its relationship to remodeling is not simply an epiphenomenon. The direct association between galectin-3 and myocardial inflammation, dysfunction, and adverse cardiovascular outcomes post-MI was examined using clinical and translational studies. METHODS: We performed expression analysis of 9753 genes in murine model of acute MI. For galectin-3 loss of function studies, homozygous galectin-3 knock-out (KO) mice were subjected to coronary artery ligation procedure to induce acute MI (MI, N = 6; Sham, N = 6). For clinical validation, serum galectin-3 levels were measured in 96 patients with ST-elevation MI. Echocardiographic and angiographic parameters of myocardial dysfunction and 3-month composite outcome including mortality, recurrent MI, stroke, and heart failure hospitalization were measured. RESULTS: In the infarct regions of murine models, galectin-3 was a robustly expressed gene. Elevated galectin-3 expression strongly correlated with macrophage-mediated genes. Galectin-3 KO mice showed reduced myocardial macrophage infiltration after acute MI. Galectin-3 levels were higher in patients with early systolic dysfunction, and predicted 3-month major adverse cardiovascular events (area under the curve [AUC]: 0.917 ± 0.063; P = .001). CONCLUSIONS: Galectin-3 is directly associated with early myocardial inflammation post-MI and may represent a potential target for therapeutic inhibition.
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spelling pubmed-59466332018-05-16 The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study Mosleh, Wassim Chaudhari, Milind R Sonkawade, Swati Mahajan, Supriya Khalil, Charl Frodey, Kevin Shah, Tanvi Dahal, Suraj Karki, Roshan Katkar, Rujuta Blankesteijn, W Matthijs Page, Brian Pokharel, Saraswati Kim, Minhyung Sharma, Umesh C Biomark Insights Original Research INTRODUCTION: Increased galectin-3 is associated with ischemic cardiomyopathy, although its role in early remodeling post-myocardial infarction (MI) has not been fully elucidated. There are no data demonstrating that blocking galectin-3 expression would have an impact on the heart and that its relationship to remodeling is not simply an epiphenomenon. The direct association between galectin-3 and myocardial inflammation, dysfunction, and adverse cardiovascular outcomes post-MI was examined using clinical and translational studies. METHODS: We performed expression analysis of 9753 genes in murine model of acute MI. For galectin-3 loss of function studies, homozygous galectin-3 knock-out (KO) mice were subjected to coronary artery ligation procedure to induce acute MI (MI, N = 6; Sham, N = 6). For clinical validation, serum galectin-3 levels were measured in 96 patients with ST-elevation MI. Echocardiographic and angiographic parameters of myocardial dysfunction and 3-month composite outcome including mortality, recurrent MI, stroke, and heart failure hospitalization were measured. RESULTS: In the infarct regions of murine models, galectin-3 was a robustly expressed gene. Elevated galectin-3 expression strongly correlated with macrophage-mediated genes. Galectin-3 KO mice showed reduced myocardial macrophage infiltration after acute MI. Galectin-3 levels were higher in patients with early systolic dysfunction, and predicted 3-month major adverse cardiovascular events (area under the curve [AUC]: 0.917 ± 0.063; P = .001). CONCLUSIONS: Galectin-3 is directly associated with early myocardial inflammation post-MI and may represent a potential target for therapeutic inhibition. SAGE Publications 2018-05-03 /pmc/articles/PMC5946633/ /pubmed/29769800 http://dx.doi.org/10.1177/1177271918771969 Text en © The Author(s) 2018 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Mosleh, Wassim
Chaudhari, Milind R
Sonkawade, Swati
Mahajan, Supriya
Khalil, Charl
Frodey, Kevin
Shah, Tanvi
Dahal, Suraj
Karki, Roshan
Katkar, Rujuta
Blankesteijn, W Matthijs
Page, Brian
Pokharel, Saraswati
Kim, Minhyung
Sharma, Umesh C
The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study
title The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study
title_full The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study
title_fullStr The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study
title_full_unstemmed The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study
title_short The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study
title_sort therapeutic potential of blocking galectin-3 expression in acute myocardial infarction and mitigating inflammation of infarct region: a clinical outcome-based translational study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946633/
https://www.ncbi.nlm.nih.gov/pubmed/29769800
http://dx.doi.org/10.1177/1177271918771969
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