Baseline Characteristics of patients with stable angina.

<p> <i>Continuous values are presented as means ± standard deviation (SD). Categorical values are presented as number (percentages).</i></p>*<p> <i>Significance level 0.05. FFR = fractional flow reserve BMI = body mass index ;DM = diabetes mellitus; MI = myocardial infarction; PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting; LVEF = left ventricular ejection fraction.</i></p>**<p> <i>Defined as a serum creatinin >150 µmol/l.</i></p

Expression levels of TLR2 and TLR4 on monocytes (A) and granulocytes (B) FFR-positive and FFR-negative patients and healthy control subjects.

<p>*Comparison by Kruskal-Wallis test for all groups.** Between subgroups with Mann Whitney U test. TLR = toll-like receptor.</p

Concentrations of cytokines and surface markers on monocytes and granulocytes according to FSS tertiles and FFR-negative patients.

<p>Concentrations of cytokines (A) and surface markers on monocytes (B) and granulocytes (C) according to FSS tertiles (of FFR-positive patients) and FFR-negative patients. Comparison of all subgroups was performed with the Jonckheere-Terpstra test. FSS = functional syntax score.</p

Comparison of levels of cytokines for FFR-positive and FFR-negative patients and healthy controls.

<p>*Comparison by Kruskal-Wallis test.** Between subgroup differences compared with Mann Whitney U test.</p

Medication use of patients with stable angina at inclusion.

<p> <i>Proportions were compared using Chi-square testing.</i></p>*<p> <i>Significance level 0.05. FFR = fractional flow reserve; ASA = Acetylsalicylic acid; ACE = angiotensin-converting enzyme.</i></p

Toll-Like Receptor Induced CD11b and L-Selectin Response in Patients with Coronary Artery Disease

<div><p>Toll-Like Receptor (TLR) -2 and -4 expression and TLR-induced cytokine response of inflammatory cells are related to atherogenesis and atherosclerotic plaque progression. We examined whether immediate TLR induced changes in CD11b and L-selectin (CD62L) expression are able to discriminate the presence and severity of atherosclerotic disease by exploring single dose whole blood TLR stimulation and detailed dose-response curves. Blood samples were obtained from 125 coronary artery disease (CAD) patients and 28 controls. CD11b and L-selectin expression on CD14+ monocytes was measured after whole blood stimulation with multiple concentrations of the TLR4 ligand LPS (0.01–10 ng/ml) and the TLR2 ligand P3C (0.5–500 ng/ml). Subsequently, dose-response curves were created and the following parameters were calculated: hillslope, EC50, area under the curve (AUC) and delta. These parameters provide information about the maximum response following activation, as well as the minimum trigger required to induce activation and the intensity of the response. CAD patients showed a significantly higher L-selectin, but not CD11b response to TLR ligation than controls after single dose stimulations as well as significant differences in the hillslope and EC50 of the dose-response curves. Within the CAD patient group, dose-response curves of L-selectin showed significant differences in the presence of hypertension, dyslipidemia, coronary occlusion and degree of stenosis, whereas CD11b expression had the strongest discriminating power after single dose stimulation. In conclusion, single dose stimulations and dose-response curves of CD11b and L-selectin expression after TLR stimulation provide diverse but limited information about atherosclerotic disease severity in stable angina patients. However, both single dose stimulation and dose-response curves of LPS-induced L-selectin expression can discriminate between controls and CAD patients.</p> </div

Dose-response curves of CAD patients and controls.

<p>Mean dose-response curves of CAD patients (dashed line) vs. controls (continuous line) for CD11b (upper panel) and L-selectin (lower panel). Samples were either stimulated with increasing concentrations of LPS (left hand panel) or P3C (right hand panel). PBS stimulation served as a control (LPS concentration = 0). Concentrations are log-transformed. Data are presented as mean ± S.E.M.</p

Single dose TLR response in relation to BMI.

<p>CD11b expression after stimulation with P3C 5 ng/ml (left) and P3C 500 ng/ml (right) was significantly higher in patients with a BMI>25 as compared to normal weight patients (BMI<25). Whiskers are presented as 5–95 percentile. Data were statistically tested with a Mann Whitney U test.</p

Dose-response curves of CAD patients in relation to clinical characteristics.

<p>A. L-selectin dose-response curves of patients with severe (>90%) coronary stenosis showed a significantly reduced hillslope and an increased AUC and delta as compared to patients with <90% stenosis. B. Responsiveness of L-selectin in patients with arterial hypertension was significantly less compared to normotensive patients indicated by a reduced AUC and a higher EC50.</p

CD11b and L-selectin expression of CAD patients and controls.

<p>Expression levels of CD11b and L-selectin of CAD patients vs. controls at baseline and after TLR stimulation. Data are presented as median [IQR].</p>*<p>p<0.05.</p>**<p>p<0.01.</p