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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doaj-75548c2906b64a9f9d53cf8ba350e30a2020-11-25T03:15:47ZengSAGE PublishingBiomarker Insights1177-27192018-05-011310.1177/1177271918771969The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational StudyWassim Mosleh0Milind R Chaudhari1Swati Sonkawade2Supriya Mahajan3Charl Khalil4Kevin Frodey5Tanvi Shah6Suraj Dahal7Roshan Karki8Rujuta Katkar9W Matthijs Blankesteijn10Brian Page11Saraswati Pokharel12Minhyung Kim13Umesh C Sharma14Division of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADepartment of Pharmacology & Toxicology, Maastricht University, Maastricht, The NetherlandsDivision of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USADepartment of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Institute, Buffalo, NY, USADepartment of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Institute, Buffalo, NY, USADivision of Cardiovascular Medicine and Clinical and Translational Research Center, University at Buffalo, Buffalo, NY, USAIntroduction: 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.https://doi.org/10.1177/1177271918771969 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wassim Mosleh Milind R Chaudhari Swati Sonkawade Supriya Mahajan Charl Khalil Kevin Frodey Tanvi Shah Suraj Dahal Roshan Karki Rujuta Katkar W Matthijs Blankesteijn Brian Page Saraswati Pokharel Minhyung Kim Umesh C Sharma |
spellingShingle |
Wassim Mosleh Milind R Chaudhari Swati Sonkawade Supriya Mahajan Charl Khalil Kevin Frodey Tanvi Shah Suraj Dahal Roshan Karki Rujuta Katkar W Matthijs Blankesteijn Brian Page Saraswati Pokharel Minhyung Kim Umesh C Sharma The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study Biomarker Insights |
author_facet |
Wassim Mosleh Milind R Chaudhari Swati Sonkawade Supriya Mahajan Charl Khalil Kevin Frodey Tanvi Shah Suraj Dahal Roshan Karki Rujuta Katkar W Matthijs Blankesteijn Brian Page Saraswati Pokharel Minhyung Kim Umesh C Sharma |
author_sort |
Wassim Mosleh |
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_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_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_sort |
therapeutic potential of blocking galectin-3 expression in acute myocardial infarction and mitigating inflammation of infarct region: a clinical outcome-based translational study |
publisher |
SAGE Publishing |
series |
Biomarker Insights |
issn |
1177-2719 |
publishDate |
2018-05-01 |
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. |
url |
https://doi.org/10.1177/1177271918771969 |
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