Abstract
BackgroundAdiponectin has insulin-sensitizing and anti-atherosclerotic effects, partly mediated through its action on monocytes. We aimed to determine adiponectin levels and expression of its receptors (AdipoR1 and AdipoR2) in peripheral monocytes from overweight and obese patients with coronary artery disease (CAD).MethodsFifty-five overweight/obese patients, suspected for CAD, underwent coronary angiography: 31 were classified as CAD patients (stenosis ≥ 50% in at least one main vessel) and 24 as nonCAD. Quantitative RT-PCR and flow cytometry were used for determining mRNA and protein surface expression of adiponectin receptors in peripheral monocytes. A high sensitivity multiplex assay (xMAP technology) was used for the determination of plasma adiponectin and interleukin-10 (IL-10) secreted levels.ResultsPlasma adiponectin levels were decreased in CAD compared to nonCAD patients (10.9 ± 3.1 vs. 13.8 ± 5.8 μg/ml respectively, p = 0.033). In multivariable analysis, Matsuda index was the sole independent determinant of adiponectin levels. AdipoR1 and AdipoR2 protein levels were decreased in monocytes from CAD compared to nonCAD patients (59.5 ± 24.9 vs. 80 ± 46 and 70.7 ± 39 vs. 95.6 ± 47.8 Mean Fluorescence Intensity Arbitrary Units respectively, p < 0.05). No significant differences were observed concerning the mRNA levels of the adiponectin receptors between CAD and nonCAD patients. AdipoR2 protein levels were positively correlated with plasma adiponectin and Matsuda index (r = 0.36 and 0.31 respectively, p < 0.05 for both). Furthermore, basal as well as adiponectin-induced IL-10 release was reduced in monocyte-derived macrophages from CAD compared to nonCAD subjects.ConclusionsOverweight patients with CAD compared to those without CAD, had decreased plasma adiponectin levels, as well as decreased surface expression of adiponectin receptors in peripheral monocytes. This fact together with the reduced adiponectin-induced IL-10 secretion from CAD macrophages could explain to a certain extent, an impaired atheroprotective action of adiponectin.
Highlights
Adiponectin has insulin-sensitizing and anti-atherosclerotic effects, partly mediated through its action on monocytes
Overweight/obese patients with coronary artery disease (CAD) were more likely to be males, while no differences were observed with regard to age, Body Mass Index (BMI), lipid profile, systolic and diastolic blood pressure compared to similar weight patients without CAD
Adiponectin receptors have been detected in human monocytes and macrophages [3,4] and recently it was found that variants of the AdipoR2 could be a determinant for atherosclerosis independent of insulin resistance [34]
Summary
Adiponectin has insulin-sensitizing and anti-atherosclerotic effects, partly mediated through its action on monocytes. AdipoR2 [1,2] These receptors are ubiquitously expressed in most organs as well as in human peripheral monocytes, and in monocyte-derived macrophages [2,3,4,5]. In these cells, adiponectin has been shown to modulate their inflammatory activity and most importantly to inhibit their transformation to foam cells, a hallmark of atherosclerosis [6,7,8,9,10]. This fact may have significant implications in terms of atherosclerotic processes, since these cells play a pivotal role in inflammation and atherosclerosis [13]
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