Monocyte toll-like receptor 2 and 4 responses and expression following percutaneous coronary intervention: association with lesion stenosis and fractional flow reserve.
BACKGROUND
Toll-like receptors (TLRs) are key players in innate immunity and are causally related to arterial occlusive disease and arterial remodelling. The release of proinflammatory cytokines following TLR ligand binding is increased in patients with unstable angina.


OBJECTIVE
To examine the effect of a percutaneous coronary intervention (PCI) on TLR2 and TLR4 response and expression.


METHODS
In 70 PCI patients, blood samples were gathered after sheath insertion and 2 hours after the catheterisation. TLR2 and TLR4 expression on, and tumour necrosis factor alpha (TNFalpha) levels in, monocytes were measured with flow cytometry. Whole blood was stimulated overnight with the TLR2 ligand Pam3Cys and the TLR4 ligand lipopolysaccharide. TNFalpha was determined in the stimulated samples and considered to be a measure of the TLR response. Baseline TLR expression and response were studied in relation to angiographic luminal stenosis and fractional flow reserve (FFR) measurement.


RESULTS
A significant relation was found between TLR response and the angiographic percentage diameter stenosis, number of diseased vessels and FFR outcome. Furthermore, 2 hours after PCI a significant decrease in TLR2 and TLR4 response (p<0.001) and TLR2 and TLR4 expression (p = 0.001 and p = 0.068, respectively) was seen.


CONCLUSIONS
TLR response is positively associated with percentage diameter stenosis, multivessel disease and FFR outcome. Systemic TLR2 and TLR4 response and expression decrease after PCI. These results suggests that the TLR signalling pathway encompasses a potential biomarker for myocardial ischaemia in stable coronary artery disease.
Versteeg
D
D
Experimental Cardiology Laboratory, University Medical Centre, Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
Hoefer
I E
IE
Schoneveld
A H
AH
de Kleijn
D P V
DP
Busser
E
E
Strijder
C
C
Emons
M
M
Stella
P R
PR
Doevendans
P A
PA
Pasterkamp
G
G
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism* / Q000502:physiology; D000789:Angina, Unstable / Q000097:blood* / Q000503:physiopathology; D001157:Arterial Occlusive Diseases / Q000097:blood* / Q000503:physiopathology; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D023921:Coronary Stenosis / Q000503:physiopathology; D005260:Female; D053805:Fractional Flow Reserve, Myocardial / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D051195:Toll-Like Receptor 2 / Q000097:blood* / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D048868:Adaptor Proteins, Signal Transducing; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha