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. CONCLUSION: 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.

On-line detection of cholesterol and calcification by catheter based Raman spectroscopy in human atherosclerotic plaque ex vivo.

BACKGROUND: Raman spectroscopy has the unique potential to detect and quantify cholesterol and calcification in an atherosclerotic plaque in vivo. OBJECTIVE: To evaluate the sensitivity and specificity of this technique for detecting cholesterol or calcification in human coronary artery and aorta specimens ex vivo, using a compact clinical fibreoptic based Raman system developed for in vivo applications. DESIGN: From nine coronary arteries and four aorta specimens, 114 sites were evaluated for the presence of cholesterol and calcification by Raman spectroscopy and standard histology. Raman spectra were acquired and evaluated on-line in around five seconds. RESULTS: The correlation between Raman spectroscopy and histology was r = 0.68 for cholesterol and r = 0.71 calcification in the plaque (p < 0.0001). Sensitivity and specificity for detecting cholesterol and calcification were excellent: receiver operating characteristic (ROC) analysis for each of the components revealed areas under the curves of > 0.92 (p < 0.0001). At the optimal cut-off values determined by ROC analysis, positive predictive values of > 80% and negative predictive values of > 90% were obtained. CONCLUSIONS: On-line real time catheter based Raman spectroscopy detects accumulation of cholesterol and calcification in atherosclerotic plaque with high sensitivity and specificity.