Pleiotropic Effects of Simvastatin on the Regulation of Potassium Channels in Monocytes
| Autor: | Shujuan Cheng, Xuejun Chen, Chungang Li, Yuhua Ran, Jinghua Liu, Shaoping Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Statin cell migration medicine.drug_class Pharmacology Peripheral blood mononuclear cell 03 medical and health sciences 0302 clinical medicine medicine Pharmacology (medical) Patch clamp cardiovascular diseases Original Research business.industry Monocyte lcsh:RM1-950 statin Cell migration Potassium channel Blot 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology Simvastatin 030220 oncology & carcinogenesis peripheral monocyte business coronary artery disease medicine.drug potassium channel |
| Zdroj: | Frontiers in Pharmacology, Vol 11 (2020) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2020.00101/full |
| Popis: | Purpose The underlying mechanism of pleiotropic effects of statins on atherosclerosis is still unclear. Kv1.3 and KCa3.1 are two potassium channels that might be involved in monocyte migration and atherosclerosis formation. The aim of this study was to investigate the effect of simvastatin on the Kv1.3 and KCa3.1 in monocyte. Methods and results In human monocytic THP-1 cells, simvastatin significantly inhibited Kv1.3 mRNA and protein expression by real-time quantitative PCR analysis and western blotting. However, simvastatin had no effects on KCa3.1 mRNA and protein expression. By whole-cell patch clamp, simvastatin (10 μM) remarkably inhibited the current intensity of Kv1.3, but had no effect on KCa3.1. Simvastatin (10 μM) treatment significantly reduced the monocyte chemoattractant protein 1 (MCP-1)-induced monocyte migration. This inhibition was only partially reversed by mevalonate (1mM). In human peripheral blood mononuclear cells (PBMCs), both Kv1.3 and KCa3.1 mRNA expression were increased in patients with coronary artery diseases (CAD) (n = 20) compared to healthy controls (n = 22). However, simvastatin (40 mg per day) significantly inhibited the Kv1.3 but not KCa3.1 mRNA expression after 1 month and 3 months therapy in CAD patients. Conclusion Our data suggested Kv1.3 in monocytes was a potential molecular target of the pleiotropic effects of statins. KCa3.1 might be another marker of CAD, but not associated with statins treatment. |
| Databáze: | OpenAIRE |
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