Leukotactin-1 Decreases the Expression of Endothelial Tight and Adherens Junction Proteins through Oxidative Stress in Human Coronary Artery Endothelial Cells

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.

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Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00329.2001 ◽

2002 ◽

Vol 282 (6) ◽

pp. L1330-L1338 ◽

Cited By ~ 62

Author(s):

D. Michael Shasby ◽

Dana R. Ries ◽

Sandra S. Shasby ◽

Michael C. Winter

Keyword(s):

Endothelial Cells ◽

Umbilical Vein ◽

Adherens Junction ◽

Vascular Endothelial ◽

Cortical Actin ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells ◽

Adherens Junction Proteins ◽

Junction Proteins

Histamine increases microvascular permeability by creating small transitory (100–400 nm) gaps between adjacent endothelial cells at sites of vascular endothelial (VE)-cadherin-based adhesion. We examined the effects of histamine on the proteins within the VE-cadherin-based adherens junction in primary human umbilical vein endothelial cells. VE-cadherin is linked not only by β- and α-catenin to cortical actin but also by γ-catenin to the intermediate filament vimentin. In mature human umbilical vein cultures, the VE-cadherin immunoprecipitate contained equivalent amounts of α- and β-catenin, 130% as much β- as γ-catenin, and 50% as much actin as vimentin. Within 60 s, histamine decreased the fraction of VE-cadherin in the insoluble portion of the cell lysate by 35 ± 1.5%. At the same time, histamine decreased the amount of vimentin that immunoprecipitated with VE-cadherin by 50 ± 6%. Histamine did not affect the amount of actin or the amount of α-, β-, or γ-catenin that immunoprecipitated with VE-cadherin. Within 60 s, histamine simulated a doubling in the phosphorylation of VE-cadherin and β- and γ-catenin. The VE-cadherin immunoprecipitate contained kinase activity that phosphorylated VE-cadherin and γ-catenin in vitro.

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

Journal of Endocrinological Investigation ◽

10.1007/s40618-014-0086-5 ◽

2014 ◽

Vol 37 (7) ◽

pp. 645-651 ◽

Cited By ~ 28

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

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00431.2009 ◽

2010 ◽

Vol 299 (1) ◽

pp. H193-H201 ◽

Cited By ~ 101

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.

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