Oxidized low-density lipoprotein (ox-LDL) is well known to disrupt normal functionality of endothelium, which plays a prominent role in endothelial dysfunction in many cardiovascular diseases. CO-releasing molecule 2 (CORM-2) is a promising candidate for treatment of cardiovascular diseases. However, it has not been defined whether CORM-2 might improve endothelial injury induced by ox-LDL. The present study was undertaken to determine the regulatory role of CORM-2 in cell injury of ox-LDL-treated human umbilical vein endothelial cells (HUVECs). Our results showed that ox-LDL inhibited the cell proliferation, but promoted apoptosis and release of cytochrome c (cytc) from mitochondrion into cytoplasm, stimulated the cleavage of caspase-3 and mitochondrial permeability transition pore (MPTP) opening. In addition, ox-LDL-incubated HUVECs exhibited excessive reactive oxygen species (ROS), increased protein levels of NADPH oxidase subunits p22phox, p47phox, NOX-2 and activation of Wnt/β-catenin signaling pathway. However, pretreatment with CORM-2 significantly reduced cell apoptosis, release of cytc from mitochondrion into cytoplasm, MPTP opening and cleavage of caspase-3, suppressed the superoxide anion generation and Wnt/β-catenin pathway activation in HUVECs response to ox-LDL. Collectively, we provide the evidence that CORM-2 attenuated ox-LDL-mediated endothelial apoptosis and oxidative stress by recovering the mitochondrial function and blocking Wnt/β-catenin pathway.
Keywords: Apoptosis; Carbon monoxide; Endothelial cell; Mitochondria; Reactive oxygen species.
Copyright © 2017 Elsevier Inc. All rights reserved.