Document Detail


Toll-like receptor 2 and 4 stimulation elicits an enhanced inflammatory response in human obese patients with atherosclerosis.
MedLine Citation:
PMID:  21446916     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The innate immune response elicited by activation of TLRs (Toll-like receptors) plays an important role in the pathogenesis of atherosclerosis. We hypothesized that cardiovascular risk factors are associated with the activation status of the innate immune system. We therefore assessed the responsiveness of TLRs on circulating cells in two groups of patients with established atherosclerosis and related this to the presence of cardiovascular risk factors. TNF (tumour necrosis factor)-α release induced by TLR2 and TLR4 activation was measured in patients with established coronary [PCI (percutaneous coronary intervention) study, n=78] or carotid artery disease [CEA (carotid endarterectomy) study, n=104], by stimulating whole blood samples with lipopolysaccharide (TLR4 ligand) and Pam3CSK4 [tripalmitoylcysteinylseryl-(lysyl)4; TLR2 ligand]. As an early activation marker, CD11b expression was measured by flow cytometry on CD14+ cells. Obesity was the 'only' risk factor that correlated with the TLR response. In both studies, obese patients had significantly higher TNF-α levels after stimulation of TLR2 compared with non-obese patients [16.9 (7.7-49.4) compared with 7.5 (1.5-19.2) pg/ml (P=0.008) in coronary artery disease and 14.6 (8.1-28.4) compared with 9.5 (6.1-15.7) pg/ml (P=0.015) in carotid artery disease; values are medians (interquartile range)]. Similar results were obtained following TLR4 stimulation. The enhanced inflammatory state in obese patients was also confirmed by a significant increased expression of the activation marker CD11b on circulating monocytes. In conclusion, obesity is associated with an enhanced TLR response in patients suffering from established atherosclerotic disease.
Authors:
Vincent P W Scholtes; Dik Versteeg; Jean-Paul P M de Vries; Imo E Hoefer; Arjan H Schoneveld; Pieter R Stella; Pieter A F M Doevendans; Karlijn J K van Keulen; Dominique P V de Kleijn; Frans L Moll; Gerard Pasterkamp
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  121     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-05-23     Completed Date:  2011-08-11     Revised Date:  2011-10-20    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  205-14     Citation Subset:  IM    
Affiliation:
Experimental Laboratory Cardiology, Department of Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Angioplasty, Balloon, Coronary
Antigens, CD11b / blood
Atherosclerosis / etiology,  immunology*
Carotid Artery Diseases / etiology,  immunology,  surgery
Cohort Studies
Coronary Artery Disease / etiology,  immunology,  therapy
Endarterectomy, Carotid
Female
Humans
Interleukin-6 / biosynthesis
Interleukin-8 / biosynthesis
Male
Middle Aged
Obesity / complications,  immunology*
Risk Factors
Toll-Like Receptor 2 / immunology*
Toll-Like Receptor 4 / immunology*
Tumor Necrosis Factor-alpha / biosynthesis
Chemical
Reg. No./Substance:
0/Antigens, CD11b; 0/ITGAM protein, human; 0/Interleukin-6; 0/Interleukin-8; 0/TLR2 protein, human; 0/TLR4 protein, human; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/Tumor Necrosis Factor-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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