Oscillating high glucose enhances oxidative stress and apoptosis in human coronary artery endothelial cells

2014 ◽  
Vol 37 (7) ◽  
pp. 645-651 ◽  
Author(s):  
Ting-song Liu ◽  
Ying-hao Pei ◽  
Yong-ping Peng ◽  
Jiao Chen ◽  
Shi-sen Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
High Glucose ◽  
Human Coronary Artery

scholarly journals Orai-IGFBP3 signaling complex regulates high-glucose exposure-induced increased proliferation, permeability, and migration of human coronary artery endothelial cells

2020 ◽  
Vol 8 (1) ◽  
pp. e001400
Author(s):  
Suwen Bai ◽  
Yuan Wei ◽  
Wenxuan Hou ◽  
YanHeng Yao ◽  
Junwei Zhu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Protein Expression ◽  
High Glucose ◽  
Barrier Function ◽  
Coronary Atherosclerosis ◽  
Human Coronary Artery ◽  
Expression Levels ◽  
Signaling Complex ◽  
Junction Protein

IntroductionDiabetes-associated endothelium dysfunction might be linked to disturbances in Ca2+ homeostasis. Our main objective is to reveal the potential mechanisms by which high-glucose (HG) exposure promotes increased proliferation of human coronary artery endothelial cells (HCAECs) in culture, and that store-operated Ca2+ entry (SOCE) and insulin-like growth factor binding protein 3 (IGFBP3) contribute to this proliferation.Research design and methodsWe detected the expression levels of Ca2+ release-activated calcium channel proteins (Orais), IGFBP3 and proliferating cell nuclear antigen of HCAECs cultured in HG medium for 1, 3, 7, and 14 days and in streptozotocin-induced diabetic mouse coronary endothelial cells. Coimmunoprecipitation and immunofluorescence technologies were used to detect the interactions between Orais and IGFBP3 of HCAECs exposed to HG environment, and to detect IGFBP3 expression and proliferation after treatment of HCAECs cultured in HG medium with an agonist or inhibitor of SOCE. Similarly, after transfection of specific small interfering RNA to knock down IGFBP3 protein expression, SOCE activity and Orais expression were tested. Some processes related to endothelial dysfunction, such as migration, barrier function and adhesion marker expression, are also measured.ResultsHG exposure promoted increased proliferation of HCAECs in culture and that SOCE and IGFBP3 contributed to this proliferation. In addition, we also found that Orais and IGFBP3 were physically associated and regulated each other’s expression levels. Besides, their expression levels and interactions were enhanced in HCAECs after exposure to HG. HG exposure promotes cell migration, but reduces barrier function and adherens junction protein expression levels in HCAECs.ConclusionOrais and IGFBP3 formed a signaling complex that mediated HCAEC proliferation during HG exposure in culture. Meanwhile, we also found that SOCE stimulates proliferation of HCAECs by regulating IGFBP3, thereby promoting the occurrence and progression of coronary atherosclerosis in diabetes. It is worth noting that our findings may shed new light on the mechanisms of increased proliferation in HCAECs in diabetes and suggest the potential value of SOCE and IGFBP3 as therapeutic targets for coronary atherosclerosis in individuals with diabetes.

scholarly journals Inhibitory Effect of a French Maritime Pine Bark Extract-Based Nutritional Supplement on TNF-α-Induced Inflammation and Oxidative Stress in Human Coronary Artery Endothelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Kristine C. Y. McGrath ◽  
Xiao-Hong Li ◽  
Lucinda S. McRobb ◽  
Alison K. Heather
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Cell Adhesion Molecule ◽  
Bark Extract ◽  
Human Coronary Artery ◽  
Cell Adhesion Molecule 1 ◽  
And Oxidative Stress

Oxidative stress and inflammation, leading to endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. The popularity of natural product supplements has increased in recent years, especially those with purported anti-inflammatory and/or antioxidant effects. The efficacy and mechanism of many of these products are not yet well understood. In this study, we tested the antioxidant and anti-inflammatory effects of a supplement, HIPER Health Supplement (HIPER), on cytokine-induced inflammation and oxidative stress in human coronary artery endothelial cells (HCAECs). HIPER is a mixture of French maritime pine bark extract (PBE), honey, aloe vera, and papaya extract. Treatment for 24 hours with HIPER reduced TNF-α-induced reactive oxygen species (ROS) generation that was associated with decreased NADPH oxidase 4 and increased superoxide dismutase-1 expression. HIPER inhibited TNF-αinduced monocyte adhesion to HCAECs that was in keeping with decreased expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1 and decreased nuclear factor-kappa B (NF-κB) activation. Further investigation of mechanism showed HIPER reduced TNF-αinduced IκBαand p38 and MEK1/2 MAP kinases phosphorylation. Our findings show that HIPER has potent inhibitory effects on HCAECs inflammatory and oxidative stress responses that may protect against endothelial dysfunction that underlies early atherosclerotic lesion formation.

scholarly journals Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells

2010 ◽  
Vol 299 (1) ◽  
pp. H193-H201 ◽  
Author(s):  
Changyi Chen ◽  
Jun Jiang ◽  
Jian-Ming Lü ◽  
Hong Chai ◽  
Xinwen Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Superoxide Dismutase ◽  
Coronary Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Human Coronary Artery ◽  
Enos Mrna ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Resistin is a newly discovered adipocyte-derived cytokine that may play an important role in insulin resistance, diabetes, adipogenesis, inflammation, and cardiovascular disease. However, it is largely unknown whether resistin impairs endothelial functions by affecting the endothelial nitric oxide synthase (eNOS) system. In this study, we determined the effect of human recombinant resistin protein on eNOS expression and regulation in human coronary artery endothelial cells (HCAECs). When cells were treated with clinically relevant concentrations of resistin (40 or 80 ng/ml) for 24 h, the levels of eNOS mRNA, protein, and activity and eNOS mRNA stability were significantly reduced. Cellular nitric oxide levels were also decreased. In addition, the cellular levels of reactive oxygen species (ROS), including superoxide anion, were significantly increased in resistin-treated HCAECs. Mitochondrial membrane potential and the activities of catalase and superoxide dismutase were reduced. Three antioxidants, seleno-l-methionine, ginsenoside Rb1, and MnTBAP (superoxide dismutase mimetic), effectively blocked resistin-induced eNOS downregulation. Meanwhile, resistin activated the mitogen-activated protein kinases p38 and c-Jun NH2-terminal kinase (JNK), and the specific p38 inhibitor SB-239063 effectively blocked resistin-induced ROS production and eNOS downregulation. Furthermore, immunoreactivity of resistin was increased in atherosclerotic regions of human aorta and carotid arteries. Thus resistin directly induces eNOS downregulation through overproduction of ROS and activation of p38 and JNK in HCAECs. Resistin-induced mitochondrial dysfunction and imbalance in cellular redox enzymes may be the underlying mechanisms of oxidative stress.

scholarly journals SUN-LB137 Endocannabinoids Induce Endoplasmic Reticulum Stress in Hepatocytes and Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Angela Richter ◽  
Shrina Parekh ◽  
Poonam Kirti Kalidas ◽  
Michael John Haas ◽  
Arshag D Mooradian
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Coronary Artery ◽  
Er Stress ◽  
High Glucose ◽  
Cannabinoid Receptor ◽  
Human Coronary Artery ◽  
Protein Kinase R ◽  
Obesity And Diabetes ◽  
In Cells

Abstract Obesity and diabetes are important risk factors for the development of coronary heart disease and stroke. Plasma endocannabinoid (EC) levels are inappropriately elevated in obesity and diabetes, and are hypothesized to play a causal role in central regulation of weight gain. Importantly, it was recently demonstrated that cannabinoid receptor 1 (CNR1) triggers cell stress and induces apoptosis in kidney tubule cells exposed to palmitic acid and high-glucose (HG). HepG2 and human coronary artery endothelial cells (HCAEC) were treated with tunicamycin (TM), thapsigargin (TG), high-glucose (HG), anandamide (AN), and 2-arachondonyl glycerol (2-AG), and endoplasmic reticulum (ER) stress was measured. In cells treated with TM, AM, and 2-AG and the UPR inhibitors 4-phenylbutyrate (4-PB) and taurodeoxycholic acid (TUDCA), both 4-PB and TUDCA prevented AN and 2-AG from promoting ER stress. ER stress in cells treated with AN and 2-AG, but not TM, was inhibited by the CNR1 antagonist rimonabant. Similar results were obtained with HCAEC. Furthermore, treatment with AN and 2-AG induced inositol requiring enzyme 1α and protein kinase R-like endoplasmic reticulum kinase phosphorylation but had no effect on their expression, while activating transcription factor 6 and binding immunoglobulin protein expression were also induced by AN and 2-AG in both HepG2 and HCAEC. Finally, AN and 2-AG treatment induced CNR1 expression in both cell lines. These results strongly suggest that EC’s promote ER stress and potentially induce liver and endothelial cell dysfunction.

scholarly journals High glucose-induced apoptosis in human coronary artery endothelial cells involves up-regulation of death receptors

2011 ◽  
Vol 10 (1) ◽  
pp. 73 ◽  
Author(s):  
Shun-ichiro Kageyama ◽  
Hiroki Yokoo ◽  
Kengo Tomita ◽  
Natsuko Kageyama-Yahara ◽  
Ryo Uchimido ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
High Glucose ◽  
Death Receptors ◽  
Human Coronary Artery ◽  
Induced Apoptosis
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