Local production of lipoprotein-associated phospholipase A2 and lysophosphatidylcholine in the coronary circulation -: Association with early coronary atherosclerosis and endothelial dysfunction in humans

Background - Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a novel marker and participant in vascular inflammation. Inflammation also is associated with coronary atherosclerosis. We tested the hypothesis that local coronary production of Lp-PLA(2) is enhanced in patients with early coronary atherosclerosis and associated with local endothelial function. Methods and Results - Coronary angiography, blood flow, flow reserve, endothelial function assessment, and intravascular ultrasound with volumetric analysis were performed in 15 patients with mild coronary atherosclerosis and in 15 control subjects. Plasma samples were collected simultaneously from the left main coronary artery and coronary sinus for measurement of Lp-PLA(2), lysophosphatidylcholine (a product of Lp-PLA(2)), and C-reactive protein. Hemodynamic parameters and cholesterol were similar in both groups. Arterial Lp-PLA(2) levels were similar in patients and control subjects: 225 ng/mL (interquartile range [IQR], 196 to 273 ng/mL) versus 221 ng/ mL ( IQR, 177 to 294 ng/mL). Lp-PLA(2) net production in the coronary circulation was higher in patients compared with control subjects: 519 ng/min (IQR, 198 to 1276 ng/min) versus -529 ng/min (IQR, -872 to -79 ng/ min; P=0.001) and correlated with percent atheroma volume (r(s) = 0.37, P = 0.04). Net production of lysophosphatidylcholine was higher in patients compared with control subjects: 199 ng/min (IQR, -592 to 470 ng/min) versus -505 ng/min (IQR, -1119 to 0 ng/min; P=0.03) and correlated with coronary endothelial dysfunction (r(s)=0.5, P=0.005). C- reactive protein was not significantly different between the groups. Conclusions - Early coronary atherosclerosis in humans is characterized by local production of Lp-PLA(2). Local coronary production of lysophosphatidylcholine, the active product of Lp-PLA(2), is associated with endothelial dysfunction. These results support the role for Lp-PLA(2) in the mechanism of regional vascular inflammation and atherosclerosis in humans.