Hyaluronic acid-dependent protection in H9C2 cardiomyocytes: A cell model of heart ischemia-reperfusion injury and treatment

Hyaluronic acid (HA), a glycosaminoglycan with high molecular weight, has been reported to promote cell proliferation and serves as an important extracellular matrix component. The aim of this study was to in vitro investigate whether HA is able to reduce reactive oxygen species (ROS)-induced heart ischemia-reperfusion injury and activate the cardiomyocyte's damage surveillance systems. Accordingly, rattus cardiomyocyte line, H9C2, was treated with H2O2 as a heart ischemia-reperfusion model followed by incubation with low molecular weight hyaluronan (LMW-HA, 100 kDa) or high molecular weight hyaluronan (HMW-HA, 1000 kDa) and proteomic analysis was performed to investigate the physiologic protection of HA in H2O2-induced ischemia-reperfusion in cardiomyocyte. Our data demonstrated that HA treatment does protect cardiomyocyte in the ROS-induced ischemia-reperfusion model and the molecular weight of HA is a crucial factor. HMW-HA has been shown to significantly facilitate cell migration and wound healing via cytoskeletal rearrangement. Additionally, 2D-DIGE combined MALDI-TOF/TOF analysis showed that HMW-HA might modulate biosynthetic pathways, cell migration, cell outgrowth and protein folding to stimulate wound healing as well as prevent these ischemia-reperfusiondamaged cardiomyocytes from cell death. To our knowledge, we report for the first time the cell repair mechanism of HMW-HA against ischemia-reperfusion-damage in cardiomyocytes based on cell biology and proteomic analysis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.