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

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

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.
Original languageEnglish
Article number1177271918771969
Pages (from-to)1–10
Number of pages10
JournalBiomarker Insights
Volume13
DOIs
Publication statusPublished - 3 May 2018

Keywords

  • Galectin-3
  • myocardial infarction
  • inflammation
  • fibrosis
  • PERCUTANEOUS CORONARY INTERVENTION
  • RENOVASCULAR HYPERTENSIVE-RATS
  • HEART-FAILURE
  • DIASTOLIC DYSFUNCTION
  • FIBROSIS
  • DISEASE
  • HYPERTROPHY
  • MACROPHAGES
  • BIOMARKERS
  • MORTALITY

Cite this