scholarly journals ASK1 Mediates Apoptosis and Autophagy during oxLDL-CD36 Signaling in Senescent Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
KyoungJoo Cho ◽  
Seung Ho Choi
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Neutralizing Antibody ◽  
Aortic Endothelial Cells ◽  
Cd36 Expression ◽  
Signaling Axis ◽  
Induced Apoptosis ◽  
Cluster Of Differentiation ◽  
Human Aortic Endothelial Cells

Vessel damage by oxidized low-density lipoprotein (oxLDL) increases reactive oxygen species (ROS) and the membrane receptor cluster of differentiation 36 (CD36), involving various vascular pathological processes. In this study, the role of apoptosis signal-regulating kinase 1 (ASK1) as a cellular effector via the oxLDL-CD36 signaling axis, and its related mechanism as a downstream responder of CD36, was investigated in senescent human aortic endothelial cells (HAECs). To inhibit oxLDL-triggered vascular damage, HAECs and monocytes were treated with the CD36-neutralizing antibody or the ASK1 inhibitor NQDI-1. The oxLDL-triggered increases in ROS and CD36 elevated active ASK1 in the senescent HAECs. The ROS increase induced apoptosis, whereas CD36 neutralization or ASK1 inhibition protected against cell death. The blocking of CD36 increased senescent HAEC autophagy. In monocytes, oxLDL also induced CD36 expression and autophagy, the latter of which still occurred following ASK1 inhibition but not after CD36 neutralization. These findings suggest that oxLDL exposure activates ASK1, as a CD36 downstream responder, to accelerate apoptosis, particularly in senescent HAECs. ASK1’s involvement in monocytic autophagy was due to endoplasmic reticulum stress resulting from the oxLDL load, suggesting that oxLDL loading on aged vessels causes atherosclerotic endothelial dysfunction mediated by active ASK1.

β-Sitosterol regulated microRNAs in endothelial cells against an oxidized low-density lipoprotein

2020 ◽  
Vol 11 (2) ◽  
pp. 1881-1890 ◽  
Author(s):  
Yue-Hua Jiang ◽  
Xiao Li ◽  
Weipin Niu ◽  
DongLi Wang ◽  
Bo Wu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Mitochondrial Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Protective Effects ◽  
Oxidized Low Density Lipoprotein ◽  
Aortic Endothelial Cells ◽  
Human Aortic Endothelial Cells

β-sitosterol is shown to demonstrate endothelial protective effects, which inhibited apoptosis, increased cell migration, and improved mitochondrial function of human aortic endothelial cells.

Low-density lipoprotein from active SLE patients is more atherogenic to endothelial cells than low-density lipoprotein from the same patients during remission

Rheumatology ◽  
2020 ◽  
Author(s):  
Ricardo Rodríguez-Calvo ◽  
Montse Guardiola ◽  
Iris Oliva ◽  
Hugo Arrando ◽  
Idoia Arranz ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Aortic Endothelial Cells ◽  
Ldl Particles ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

Abstract Objectives SLE patients have an enhanced risk of atherosclerosis and cardiovascular disease. However, the increased prevalence of cardiovascular disease is not fully explained by traditional Framingham cardiovascular risk factors. Specific features of low-density lipoprotein (LDL) particles, other than plasma concentration, may induce accelerated atherosclerosis at early stages in these patients. Thus, we aimed to explore the impact of LDL from both active and inactive SLE patients on human aortic endothelial cells. Methods Human aortic endothelial cells were stimulated with the same concentration of LDL particles isolated from pooled serum that was collected from 13 SLE patients during both active and inactive states. Gene expression and cell migration assays were performed. Results Circulating LDL particles obtained from healthy volunteers and SLE patients in both remission and flare states were comparable in terms of number, cholesterol and triglyceride content, and net electric charge. Stimulation of cells with LDL from active SLE patients induced the expression of vascular cell adhesion molecule 1 (∼2.0-fold, P < 0.05), monocyte chemoattractant protein 1 (∼2.0-fold, P < 0.05) and matrix metallopeptidase 2 (∼1.6-fold, P < 0.01) compared with cells stimulated with LDL from inactive SLE patients. Additionally, LDL extracted from active patients increased cell migration in a wound-healing assay (1.4-fold, P < 0.05). Conclusion Our data show that, at the same LDL concentration, LDL from active SLE patients had increased proatherogenic effects on endothelial cells compared with LDL from the same patients when in an inactive or remission state.

scholarly journals TNF-α Activates High-Mobility Group Box 1 - Toll-Like Receptor 4 Signaling Pathway in Human Aortic Endothelial Cells

2016 ◽  
Vol 38 (6) ◽  
pp. 2139-2151 ◽  
Author(s):  
Won Seok Yang ◽  
Nam Jeong Han ◽  
Jin Ju Kim ◽  
Mee Jeong Lee ◽  
Su-Kil Park
Keyword(s):  
Signal Transduction ◽  
Endothelial Cells ◽  
High Mobility ◽  
Neutralizing Antibody ◽  
High Mobility Group ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Aortic Endothelial Cells ◽  
Tnf Α ◽  
Human Aortic Endothelial Cells

Background/Aims: Toll-like receptor 4 (TLR4) interacts with endogenous substances as well as lipopolysaccharide. We explored whether TLR4 is implicated in tumor necrosis factor-α (TNF-α) signal transduction in human aortic endothelial cells. Methods: The pathway was evaluated by transfection of siRNAs, immunoprecipitation and Western blot analysis. Results: TNF-α activated spleen tyrosine kinase (Syk) within 10 min, which led to endothelin-1 (ET-1) production. TLR4 was also rapidly activated by TNF-α stimulation, as shown by recruitment of interleukin-1 receptor-associated kinase 1 to TLR4 and its adaptor molecule, myeloid differentiation factor 88 (MyD88). siRNA depletion of TLR4 markedly attenuated TNF-α-induced Syk activation and ET-1 production. TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody and siRNA depletion of MyD88 also attenuated TNF-α-induced Syk activation. Syk was co-immunoprecipitated with TLR4, and TNF-α activated Syk bound to TLR4. High-mobility group box 1 (HMGB1) was rapidly released and associated with TLR4 after TNF-α stimulation with a peak at 5 min, which was prevented by N-acetylcysteine, an antioxidant. Glycyrrhizin (HMGB1 inhibitor), HMGB1-neutralizing antibody and siRNA depletion of HMGB1 all suppressed TNF-α-induced Syk activation and ET-1 production. Conclusion: Upon TNF-α stimulation, TLR4 is activated by HMGB1 that is immediately released after the generation of reactive oxygen species, and plays a crucial role in the signal transduction.

scholarly journals High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature

2016 ◽  
Vol 112 (3) ◽  
pp. 656-668 ◽  
Author(s):  
Fulong Wang ◽  
Jocelyn Jia ◽  
Nathaniel Lal ◽  
Dahai Zhang ◽  
Amy Pei-Ling Chiu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
High Glucose ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Neutralizing Antibody ◽  
Metabolic Adaptation ◽  
Rat Cardiomyocytes ◽  
Altered Expression ◽  
And Function

Aims The secretion of enzymatically active heparanase (HepA) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (HepL) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of HepL from the endothelial cell (EC), HepL uptake and function can protect the cardiomyocyte by modifying its cell death signature. Methods and results HG promoted both HepL and HepA secretion from microvascular (rat heart micro vessel endothelial cells, RHMEC) and macrovascular (rat aortic endothelial cells, RAOEC) EC. However, only RAOEC were capable of HepL reuptake. This occurred through a low-density lipoprotein receptor-related protein 1 (LRP1) dependent mechanism, as LRP1 inhibition using small interfering RNA (siRNA), receptor-associated protein, or an LRP1 neutralizing antibody significantly reduced uptake. In cardiomyocytes, which have a negligible amount of heparanase gene expression, LRP1 also participated in the uptake of HepL. Exogenous addition of HepL to rat cardiomyocytes produced a dramatically altered expression of apoptosis-related genes, and protection against HG and H2O2 induced cell death. Cardiomyocytes from acutely diabetic rats demonstrated a robust increase in LRP1 expression and levels of heparanase, a pro-survival gene signature, and limited evidence of cell death, observations that were not apparent following chronic and progressive diabetes. Conclusion Our results highlight EC-to-cardiomyocyte transfer of heparanase to modulate the cardiomyocyte cell death signature. This mechanism was observed in the acutely diabetic heart, and its interruption following chronic diabetes may contribute towards the development of diabetic cardiomyopathy.

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