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Clopidogrel Effectively Suppresses Endothelial Microparticle Generation Induced by Indoxyl Sulfate via Inhibition of the p38 Mitogen-Activated Protein Kinase Pathway.
MedLine Citation:
PMID:  21811066     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background/Aims: Endothelial microparticles (EMPs) are closely associated with vascular dysfunction. We investigated the effects of several drugs on EMP generation in human umbilical vein endothelial cells (HUVECs), and the involvement of the mitogen-activated protein kinase (MAPK) in EMP generation. Methods: CD31+CD42-EMP counts were measured by flow cytometry in supernatants of HUVECs incubated with indoxyl sulfate. The EMP responses to losartan, lovastatin, clopidogrel, and mesoglycan were examined. We then measured the effects of MAPK inhibitors on EMPs. Results: (1) Indoxyl sulfate induced EMP release in HUVECs in a dose-dependent fashion; (2) all drugs (10-50 μM) inhibited EMP generation induced by indoxyl sulfate, with clopidogrel being the most effective; (3) the p38 MAPK inhibitor suppressed EMP generation induced by indoxyl sulfate, and (4) clopidogrel significantly suppressed MAPK signaling activated by indoxyl sulfate, with the most potency on p38. Conclusion: The p38 signaling involves EMP generation induced by indoxyl sulfate and is effectively suppressed by clopidogrel.
Authors:
Jung-Hwa Ryu; Seung-Jung Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-29
Journal Detail:
Title:  Blood purification     Volume:  32     ISSN:  1421-9735     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-8-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8402040     Medline TA:  Blood Purif     Country:  -    
Other Details:
Languages:  ENG     Pagination:  186-194     Citation Subset:  -    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Division of Nephrology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
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