Ox-LDL induces apoptosis in human coronary artery endothelial cells: role of PKC, PTK, bcl-2, and Fas

1998 ◽  
Vol 275 (2) ◽  
pp. H568-H576 ◽  
Author(s):  
Dayuan Li ◽  
Baichun Yang ◽  
Jawahar L. Mehta
Keyword(s):  
Endothelial Cells ◽  
Protein Tyrosine Kinase ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Light And Electron Microscopy ◽  
Density Lipoprotein ◽  
Human Coronary Artery ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Hypoxia Reoxygenation

Oxidized low-density lipoprotein (ox-LDL) plays a critical role in the development of atherosclerosis. Recent studies show that ox-LDL may induce apoptosis of cultured rabbit smooth muscle cells and human macrophages. This study was designed to determine the modulation by ox-LDL of apoptosis in cultured human coronary arterial endothelial cells (HCAEC) during hypoxia-reoxygenation and to determine underlying mechanisms. When HCAEC were ∼85% confluent, the cells were exposed to hypoxia (24 h)-reoxygenation (3 h), native LDL, or ox-LDL. Fragmented DNA end-labeling, DNA laddering, and light and electron microscopy were used to determine changes characteristic of apoptosis. Ox-LDL (20 μg/ml) increased apoptosis during hypoxia-reoxygenation compared with hypoxia-reoxygenation alone ( P < 0.05). Low concentrations of ox-LDL (5 μg/ml) and native LDL (20 μg/ml) under identical conditions had no effect on the degree of apoptosis. Ox-LDL markedly decreased endogenous superoxide dismutase activity and increased lipid peroxidation in HCAEC. The presence of ox-LDL, but not native LDL, in cultured HCAEC resulted in the activation of protein kinase C (PKC) and protein tyrosine kinase (PTK). The specific PKC and PTK inhibitors significantly reduced ox-LDL-mediated apoptosis of HCAEC ( P < 0.05). Hypoxia-reoxygenation significantly increased Fas expression and decreased bcl-2 expression in HCAEC lysate as determined by Western analysis. Ox-LDL further increased Fas expression and decreased bcl-2 expression. These data indicate that ox-LDL enhances hypoxia-reoxygenation-mediated apoptosis in HCAEC. Ox-LDL-mediated apoptosis of HCAEC appears to involve activation of PKC and PTK. In addition, ox-LDL modulates Fas and bcl-2 protein expression in HCAEC. This study also suggests that ox-LDL is more important than native LDL in hypoxia-reoxygenation-induced apoptosis.

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.

scholarly journals Effects of Equol on Oxidized Low-Density Lipoprotein-Induced Apoptosis in Endothelial Cells

2009 ◽  
Vol 16 (3) ◽  
pp. 239-249 ◽  
Author(s):  
Masumi Kamiyama ◽  
Yoshimi Kishimoto ◽  
Mariko Tani ◽  
Kazunori Utsunomiya ◽  
Kazuo Kondo
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Induced Apoptosis

Phosphocreatine protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

APOPTOSIS ◽  
2015 ◽  
Vol 20 (12) ◽  
pp. 1563-1576 ◽  
Author(s):  
Anil Ahsan ◽  
Guozhu Han ◽  
Junfang Pan ◽  
Shumin Liu ◽  
Arshad Ahmed Padhiar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Induced Apoptosis

A Caspase Inhibitor Decreases Oxidized Low-Density Lipoprotein-Induced Apoptosis in Bovine Endothelial Cells

1999 ◽  
Vol 85 (2) ◽  
pp. 323-330 ◽  
Author(s):  
Alik Farber ◽  
Tamar Kitzmiller ◽  
Peter M. Morganelli ◽  
Jason Pfeiffer ◽  
Debra Groveman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Caspase Inhibitor ◽  
Oxidized Low Density Lipoprotein ◽  
Bovine Endothelial Cells ◽  
Induced Apoptosis

scholarly journals Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transcriptional regulation by Oct-1 in human endothelial cells: implications for atherosclerosis

2005 ◽  
Vol 393 (1) ◽  
pp. 255-265 ◽  
Author(s):  
Jiawei Chen ◽  
Yong Liu ◽  
Hongmei Liu ◽  
Paul L. Hermonat ◽  
Jawahar L. Mehta
Keyword(s):  
Endothelial Cells ◽  
Core Promoter ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Binding Motif ◽  
Low Density ◽  
Ang Ii ◽  
Oxidized Low Density Lipoprotein ◽  
Promoter Activation

LOX-1, a receptor for ox-LDL (oxidized low-density lipoprotein), has recently been determined to play a critical role in the progression of atherosclerosis. LOX-1 expression (mRNA and protein) has been shown to be up-regulated by pro-atherogenic stimuli, such as ox-LDL and Ang II (angiotensin II). However, the molecular mechanisms of these up-regulations are unclear. In the present study, we explored LOX-1 transcriptional promoter activation in response to ox-LDL and Ang II. Under basal states, LOX-1 core promoter (LOX-1 −35/+36) was found to be sufficient for its basal activity in HCAECs (human coronary artery endothelial cells). More importantly, we found that ox-LDL (60 μg/ml for 24 h) induced LOX-1 promoter activity significantly and that a 105 bp fragment (between nt −1599 and −1494) was required for this activation. Within this 106 bp fragment, there is a potential binding motif for the transcription factor Oct-1 (octamer-1). By electrophoretic mobility-shift assay, we observed the activation of Oct-1 by ox-LDL. The critical role of Oct-1 in ox-LDL-induced LOX-1 promoter activation was further confirmed by mutagenesis assay. For comparison, we also examined LOX-1 promoter activation in response to Ang II (1 μmol/l for 24 h). Interestingly, another promoter region, between nt −2336 and −1990, was required for Ang II-induced LOX-1 promoter activation. In conclusion, the present study strongly suggests that ox-LDL, by activating Oct-1, induces LOX-1 promoter activation. Furthermore, this study suggests that while ox-LDL and Ang II both induce LOX-1 expression in HCAECs, the underlying mechanisms of promoter activation are different from each other.

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