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(Circulation. 2007;115:2715-2721.)
© 2007 American Heart Association, Inc.

Coronary Heart Disease

Local Production of Lipoprotein-Associated Phospholipase A₂ and Lysophosphatidylcholine in the Coronary Circulation

Association With Early Coronary Atherosclerosis and Endothelial Dysfunction in Humans

Shahar Lavi, MD; Joseph P. McConnell, PhD; Charanjit S. Rihal, MD; Abhiram Prasad, MD; Verghese Mathew, MD; Lilach O. Lerman, MD, PhD; Amir Lerman, MD

From the Division of Cardiovascular Diseases (S.L., C.S.R., A.P., V.M., L.O.L., A.L.), Department of Laboratory Medicine and Pathology (J.P.M.), and Division of Nephrology and Hypertension (L.O.L.), Mayo Clinic, Rochester, Minn.

Correspondence to Amir Lerman, MD, Division of Cardiovascular Diseases, Mayo Clinic, Mary Brigh 4–523, First St SW, Rochester, MN 55905. E-mail Lerman.Amir{at}mayo.edu

Received October 19, 2006; accepted March 26, 2007.

Background— Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) 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-PLA₂ 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-PLA₂, lysophosphatidylcholine (a product of Lp-PLA₂), and C-reactive protein. Hemodynamic parameters and cholesterol were similar in both groups. Arterial Lp-PLA₂ 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-PLA₂ 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-PLA₂. Local coronary production of lysophosphatidylcholine, the active product of Lp-PLA₂, is associated with endothelial dysfunction. These results support the role for Lp-PLA₂ in the mechanism of regional vascular inflammation and atherosclerosis in humans.

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