Donepezil Prevents ox-LDL-Induced Attachment of THP-1 Monocytes to Human Aortic Endothelial Cells (HAECs)
| Autor: | Sheng Wang, Guobao Zhang, Peng Liu, Shengkai Zhou, Zhao Li, Jian Zhao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Endothelium
medicine.drug_class Pharmacology Protective Agents Toxicology Monocytes Pathogenesis Structure-Activity Relationship Tissue factor Downregulation and upregulation mental disorders medicine Humans Donepezil THP1 cell line Aorta Cells Cultured Dose-Response Relationship Drug Molecular Structure Chemistry Endothelial Cells General Medicine Lipoproteins LDL medicine.anatomical_structure Acetylcholinesterase inhibitor Lipoprotein medicine.drug |
| Zdroj: | Chemical Research in Toxicology. 33:975-981 |
| ISSN: | 1520-5010 0893-228X |
| Popis: | Oxidized low-density lipoprotein (ox-LDL)- induced endothelial insults plays an important role in the pathogenesis of atherosclerosis. Donepezil is a well-known acetylcholinesterase inhibitor with its primary application being the treatment of Alzheimer's disease. More recently, there has been increased interest in donepezil as an antiatherosclerosis treatment as it possesses a host of relevant and potentially beneficial properties. In the present study, we found that donepezil could reduce the expression of lectin-type oxidized low-density lipoprotein receptor-1 (LOX-1) in human aortic endothelial cells (HAECs). We found that donepezil could suppress the expression of intercellular adhesion molecule-1 (ICAM-1), which recruits monocytes to adhere to the endothelium, by more than half. Another key finding of our study is that donepezil could reduce the expression of tumor necrosis factor receptor-α (TNF-α) and interleukin-6 (IL-6) by more than half at both the mRNA and protein transcriptional levels. Donepezil also reduced the expression of tissue factor (TF), which is considerably upregulated in atherosclerotic lesions, by more than half. Finally, we turned our attention to the early growth response protein-1 (Egr-1) for its potential role in mediating the effects of donepezil. Through our Egr-1 overexpression experiment, we found that overexpression of Egr-1 almost completely abolished the effects of donepezil described above. Thus, the effects of donepezil are likely mediated through downregulation of Egr-1. These findings provide evidence that donepezil may exert protective effects against atherosclerosis. |
| Databáze: | OpenAIRE |
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