4P-0990 Mulberry leaf extracts inhibit expression of lectin-like oxidized LDL receptor-1 (LOX-1) in vascular endothelial cells

Plasminogen activator inhibitor-1 (PAI-1) is implicated in thrombogenesis, inflammation, and extracellular matrix remodeling. Previous studies indicated that oxidized low-density lipoprotein (LDL) stimulated the generation of PAI-1 in vascular endothelial cells (EC). The present study demonstrated that LDL oxidized by copper, iron, or 3-morpholinosydnonimine increased the expression of NADPH oxidase (NOX) 2, PAI-1, and heat shock factor-1 (HSF1) in human umbilical vein EC or coronary artery EC compared with LDL or vehicle. Diphenyleneiodonium, a NOX inhibitor, prevented the increases of the expression of HSF1 and PAI-1 in EC induced by oxidized LDLs. Small-interference RNA (siRNA) for p22phox, an essential subunit of NOX, prevented oxidized LDL-induced expression of NOX2, HSF1, and PAI-1 in EC. HSF1 siRNA inhibited oxidized LDL-induced expression of PAI-1 and HSF1, but not NOX2, in EC. The binding of HSF1 to PAI-1 promoter and the activity of PAI-1 promoter in EC were enhanced by oxidized LDL. Butylated hydroxytulene, a potent antioxidant, inhibited oxidized LDL-induced release of hydrogen peroxide (H2O2) and the expression of NOX2, HSF1, and PAI-1 in EC. Treatment with H2O2 increased the abundance of NOX2, HSF1, and PAI-1 in EC. The results of the present study indicate that oxidized LDL-induced expression of NOX may lead to the elevated release of reactive oxygen species, the activation of HSF1, and the enhancement of the transcription of PAI-1 gene in cultured vascular EC.

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Statins Attenuate Activation of the NLRP3 Inflammasome by Oxidized LDL or TNFα in Vascular Endothelial Cells through a PXR-Dependent Mechanism

Molecular Pharmacology ◽

10.1124/mol.116.108100 ◽

2017 ◽

Vol 92 (3) ◽

pp. 256-264 ◽

Cited By ~ 25

Author(s):

Shaolan Wang ◽

Xinya Xie ◽

Ting Lei ◽

Kang Zhang ◽

Baochang Lai ◽

...

Keyword(s):

Endothelial Cells ◽

Nlrp3 Inflammasome ◽

Vascular Endothelial Cells ◽

Oxidized Ldl ◽

Vascular Endothelial ◽

Dependent Mechanism

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Effects of Oxidized LDL on Platelet Aggregation and Vascular Endothelial Cells

The Showa University Journal of Medical Sciences ◽

10.15369/sujms1989.2.1 ◽

1990 ◽

Vol 2 (1) ◽

pp. 1-5

Author(s):

Tsuneaki OGAWA ◽

Seishi NAGANO ◽

Terumi TAKAHASHI

Keyword(s):

Endothelial Cells ◽

Platelet Aggregation ◽

Vascular Endothelial Cells ◽

Oxidized Ldl ◽

Vascular Endothelial

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Targeting Gene Transfer Selectively to Vascular Endothelial Cells Using Peptides Isolated by Phage Display: Implications for Development of Gene Therapy in Hypertension

Hypertension ◽

10.1161/hyp.36.suppl_1.691-c ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 691-691

Author(s):

Stuart A Nicklin ◽

Steve J White ◽

Andrew H Baker

Keyword(s):

Endothelial Cells ◽

Gene Transfer ◽

Phage Display ◽

Vascular Endothelial Cells ◽

Ldl Receptor ◽

Vascular Endothelial ◽

Single Chain ◽

Single Chain Antibody ◽

Adenoviral Gene Transfer ◽

Low Efficiency

75 Current gene transfer vectors are extremely limited for selective vascular cell delivery due to their promiscuous tropism and low efficiency of gene delivery to the vasculature. We have sought to improve the efficiency of gene transfer to vascular endothelial cells using phage display. Using bio-panning on whole cells, we have isolated a panel of 60 7-mer peptides that have the ability to bind endothelial cells but not to non-endothelial cells including vascular smooth muscle cells and hepatocytes. One candidate peptide was cloned upstream of a single chain antibody (scFv) generated against the knob domain of adenovirus type 5, expressed in bacteria and purified. While the scFv alone inhibited adenoviral fiber-dependent infection of all cell types tested (to >95% in hepatocytes), the scFv-peptide fusion mediated selective infection into endothelial cells without infection into non-endothelial cells types. Furthermore, the level of infection achieved in endothelial cells was 15 fold higher than that achieved with fiber-mediated gene transfer alone. We have additionally isolated 15 individual peptides that have the ability to target the endothelial leptin-like oxidised LDL receptor (LOX-1), a receptor highly expressed in endothelial cells in hypertensive models and in atherosclerotic lesions, by phage bio-panning on cells ectopically expressing the LOX-1 receptor. Candidate peptides mediated significantly higher binding to LOX-1 expressing cells compared to LOX-1 negative cells. Their ability to re-target adenoviral gene transfer is being tested. Our results demonstrate that small, novel peptides isolated by phage display have the ability to retarget gene transfer selectively and efficiently to vascular endothelial cells. This has important implications for targeting gene transfer to endothelial cells for molecular and therapeutic protocols in hypertension.

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