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Biomark Insights. 2018 May 3;13:1177271918771969. doi: 10.1177/1177271918771969. eCollection 2018.

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

Author information

1
Division of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, NY, USA.
2
Department of Pharmacology & Toxicology, Maastricht University, Maastricht, The Netherlands.
3
Department of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Institute, Buffalo, NY, USA.
4
Division of Cardiovascular Medicine and Clinical and Translational Research Center, University at Buffalo, Buffalo, NY, USA.

Abstract

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.

KEYWORDS:

Galectin-3; fibrosis; inflammation; myocardial infarction

Conflict of interest statement

Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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