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Title: CO-releasing molecules-2 attenuates ox-LDL-induced injury in HUVECs by ameliorating mitochondrial function and inhibiting Wnt/β-catenin pathway

Abstract

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 p22{sup phox}, p47{sup phox}, 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. - Highlights: • CORM-2more » ameliorated ox-LDL-induced apoptosis, mitochondrial damage, and Wnt/β-catenin activation in HUVECs. • CORM-2 is potential therapeutic agent against endothelial dysfunction-related diseases.« less

Authors:
; ; ; ; ; ;  [1];  [2]
  1. Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122 (China)
  2. Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004 (China)
Publication Date:
OSTI Identifier:
22719045
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 490; Journal Issue: 3; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CARBON; CARBON MONOXIDE; CARDIOVASCULAR DISEASES; CELL PROLIFERATION; CHANNELING; CYTOCHROMES; CYTOPLASM; ENDOTHELIUM; INJURIES; LIPOPROTEINS; MITOCHONDRIA; OXIDASES; OXIDATION; PERMEABILITY; VEINS

Citation Formats

Sun, Hai-Jian, Xu, Dong-Yan, Sun, Yi-Xin, Xue, Tong, Zhang, Chen-Xing, Zhang, Zhi-Xuan, Lin, Wei, and Li, Ke-Xue. CO-releasing molecules-2 attenuates ox-LDL-induced injury in HUVECs by ameliorating mitochondrial function and inhibiting Wnt/β-catenin pathway. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.06.089.
Sun, Hai-Jian, Xu, Dong-Yan, Sun, Yi-Xin, Xue, Tong, Zhang, Chen-Xing, Zhang, Zhi-Xuan, Lin, Wei, & Li, Ke-Xue. CO-releasing molecules-2 attenuates ox-LDL-induced injury in HUVECs by ameliorating mitochondrial function and inhibiting Wnt/β-catenin pathway. United States. doi:10.1016/J.BBRC.2017.06.089.
Sun, Hai-Jian, Xu, Dong-Yan, Sun, Yi-Xin, Xue, Tong, Zhang, Chen-Xing, Zhang, Zhi-Xuan, Lin, Wei, and Li, Ke-Xue. Sat . "CO-releasing molecules-2 attenuates ox-LDL-induced injury in HUVECs by ameliorating mitochondrial function and inhibiting Wnt/β-catenin pathway". United States. doi:10.1016/J.BBRC.2017.06.089.
@article{osti_22719045,
title = {CO-releasing molecules-2 attenuates ox-LDL-induced injury in HUVECs by ameliorating mitochondrial function and inhibiting Wnt/β-catenin pathway},
author = {Sun, Hai-Jian and Xu, Dong-Yan and Sun, Yi-Xin and Xue, Tong and Zhang, Chen-Xing and Zhang, Zhi-Xuan and Lin, Wei and Li, Ke-Xue},
abstractNote = {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 p22{sup phox}, p47{sup phox}, 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. - Highlights: • CORM-2 ameliorated ox-LDL-induced apoptosis, mitochondrial damage, and Wnt/β-catenin activation in HUVECs. • CORM-2 is potential therapeutic agent against endothelial dysfunction-related diseases.},
doi = {10.1016/J.BBRC.2017.06.089},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 490,
place = {United States},
year = {2017},
month = {8}
}