Monocyte toll-like Receptor 2 and 4 responses and expression following percutaneous coronary intervention: Association with lesion stenosis and fractional flow reserve

Dik Versteeg ¹, Imo Hoefer ¹, Arjan Schoneveld ¹, Dominique de Kleijn ¹, Els Busser ¹, Chaylendra Strijder ¹, Maringa Emons ¹, Pieter Stella ¹, Pieter Doevendans ¹ and Gerard Pasterkamp ^1*

¹ University Medical Center Utrecht, Netherlands

^* To whom correspondence should be addressed. E-mail: g.pasterkamp{at}umcutrecht.nl.

Accepted 17 July 2007

Abstract

Background Toll-like receptors (TLRs) are key players in innate immunity and are causally related to arterial occlusive disease and arterial remodeling. The release of pro-inflammatory cytokines following TLR ligand binding is increased in patients with unstable angina. We examined 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 catheterization. TLR2 and TLR4 expression on, and TNF- levels in monocytes were measured with flowcytometry. Whole blood was stimulated overnight with the TLR2 ligand Pam3Cys and the TLR4 ligand lipopolysaccharide (LPS). TNF- was determined in the stimulated samples and considered 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 We observed a significant relation between TLR response and the angiographic percentage diameter stenosis, number of diseased vessels and FFR outcome. Furthermore two hours after PCI we observed a significant decrease in TLR2 and TLR4 response (p<0.001) and TLR2 and TLR4 expression (p=0.001 and p=0.068 respectively).

Conclusion TLR response is positively associated with percentage diameter stenosis, multivessel disease and FFR outcome. Systemic TLR2 and TLR4 response and expression decrease following PCI. These results suggests that the TLR signaling pathway encompasses a potential biomarker for myocardial ischemia in stable coronary artery disease.

Keywords: angioplasty, catheterization, coronary disease, immune system, inflammation

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