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

Autor: 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
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Biomarker Insights, Vol 13 (2018)
Druh dokumentu: article
ISSN: 1177-2719
11772719
DOI: 10.1177/1177271918771969
Popis: 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.
Databáze: Directory of Open Access Journals
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