These authors contributed equally to this work.
Phloretin suppresses thrombin-mediated leukocyte-platelet-endothelial interactions
Article first published online: 16 DEC 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 4, pages 698–708, April 2014
How to Cite
Kim, M. S., Park, S.-H., Han, S.-Y., Kim, Y.-H., Lee, E.-J., Yoon Park, J. H. and Kang, Y.-H. (2014), Phloretin suppresses thrombin-mediated leukocyte-platelet-endothelial interactions. Mol. Nutr. Food Res., 58: 698–708. doi: 10.1002/mnfr.201300267
- Issue published online: 1 APR 2014
- Article first published online: 16 DEC 2013
- Manuscript Accepted: 25 SEP 2013
- Manuscript Revised: 19 SEP 2013
- Manuscript Received: 16 APR 2013
- Ministry of Education, Science Technology (MEST). Grant Number: 2012R1A2A2A01012946
- Protease-activated receptor-1;
Thrombin playing a pivotal role in coagulation cascade may influence the onset and progression of atherosclerosis as a pro-inflammatory mediator. This study investigated whether phloretin found in apple tree leaves, severed a linkage between thrombosis and atherosclerosis by thrombin.
Methods and results
Human endothelial cells were pre-treated with 1–20 μM phloretin and stimulated with 10 U/mL thrombin. Phloretin attenuated adhesion of THP-1 monocytes and platelets to thrombin-inflamed endothelial cells with concurrent inhibition of protease-activated receptor (PAR-1) induction. The thrombin induction of endothelial CD40, endothelial integrin β3 and P-selectin, and monocytic CD40L was dampened by phloretin. Additionally, phloretin inhibited monocyte secretion of MCP-1, IL-6 and IL-8 responsible for pro-inflammatory activity of thrombin inducing endothelial CD40. The monocyte COX-2 induction and PGE2 secretion due to thrombin were down-regulated by phloretin, deterring endothelial CD40 expression. Thrombin promoted production of PAI-1 and tissue factor in monocytes was attenuated by phloretin through blocking PAR-1 and CD40. Thrombin up-regulated the induction of endothelial connective tissue growth factor independent of PAR-1 activation, which was reversed by phloretin.
Phloretin disturbed tethering and stable adhesion of monocytes and platelets onto endothelium during increased thrombosis by thrombin. Phloretin would be a potent agent preventing thrombosis and atherosclerosis.