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.
Skip Nav Destination
Article navigation
Research Article|
May 20 2011
Toll-like receptor 2 and 4 stimulation elicits an enhanced inflammatory response in human obese patients with atherosclerosis
Vincent P.W. Scholtes;
Vincent P.W. Scholtes
*Experimental Laboratory Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for other works by this author on:
Dik Versteeg;
Dik Versteeg
†Department of Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for other works by this author on:
Jean-Paul P.M. de Vries;
Jean-Paul P.M. de Vries
‡Department of Vascular Surgery, St Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
Search for other works by this author on:
Imo E. Hoefer;
Imo E. Hoefer
*Experimental Laboratory Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for other works by this author on:
Arjan H. Schoneveld;
Arjan H. Schoneveld
*Experimental Laboratory Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
§Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for other works by this author on:
Pieter R. Stella;
Pieter R. Stella
‖Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
Search for other works by this author on:
Pieter A.F.M. Doevendans;
Pieter A.F.M. Doevendans
‖Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
Search for other works by this author on:
Karlijn J.K. van Keulen;
Karlijn J.K. van Keulen
*Experimental Laboratory Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for other works by this author on:
Dominique P.V. de Kleijn;
Dominique P.V. de Kleijn
*Experimental Laboratory Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
Search for other works by this author on:
Frans L. Moll;
Frans L. Moll
¶Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
Search for other works by this author on:
Gerard Pasterkamp
*Experimental Laboratory Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
Correspondence: Professor Gerard Pasterkamp (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 05 2011
Revision Received:
March 15 2011
Accepted:
March 29 2011
Accepted Manuscript online:
March 29 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 121 (5): 205–214.
Article history
Received:
January 05 2011
Revision Received:
March 15 2011
Accepted:
March 29 2011
Accepted Manuscript online:
March 29 2011
Citation
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; Toll-like receptor 2 and 4 stimulation elicits an enhanced inflammatory response in human obese patients with atherosclerosis. Clin Sci (Lond) 1 September 2011; 121 (5): 205–214. doi: https://doi.org/10.1042/CS20100601
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |