Indocyanine Green-001 (ICG-001) Attenuates Wnt/β-catenin-induces Myocardial Injury Following Sepsis.

Abstract

Objective:To investigate the mechanistic pathway of both indocyanine green (ICG)-001 in attenuated endotoxemia-induced cardiac depression through downregulation cardiac Wnt/ β-catenin cell signaling.Materials and Methods:Adult (4–6 months) male Albino-Webster mice, their weights ranged from 25 to 30 g, were pretreated with ICG-001 i.p., following cecal ligation and puncture (CLP). Left ventricle (LV) function was assessed using a microcatheter system. Monocyte chemoattractant protein-1 (MCP-1) and cytokines mediators in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay. Further, the cardiac Wnt protein measured by quantitative real-time polymerase chain reaction while β-catenin analysis through Western blotting procedure. The pathological changes and cells injury in the myocardium were examined using hematoxylin and eosin staining.Results:CLP mice displayed worse LV function. The exaggerated cardiac depression in CLP mice was associated with higher levels of MCP-1 and cytokines in plasma and myocardium together with greater cardiac levels of cardiac troponin-I and Wnt/β-catenin. Neutralization of sepsis by either ICG-001resulted in improved LV function and reductions in inflammatory mediators.Conclusion:Taken together, these data showed that ICG-001 improved LV function following sepsis through downregulation of Wnt/β-catenin and serve as a potential mechanistic pathway ICG-001 in therapeutic cardiac endotoxemia in animal model.