Objective-The purpose of the current study was to determine whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 )is associated with coronary endothelial dysfunction and is a predictor of endothelial dysfunction in humans. Methods and Results-Patients (172) with no significant coronary artery disease (Ͻ30% stenosis) undergoing assessment of coronary endothelial function were studied. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Plasma concentrations of Lp-PLA 2 were measured, and patients were divided into tertiles. Patients in tertiles 2 and 3 had a significantly lower change in coronary blood flow (63. C oronary artery disease is the leading cause of morbidity and mortality in Western society and is a worldwide epidemic. The identification of patients at risk for coronary events and those in the early stages of atherosclerosis is essential for primary prevention. Predicting cardiac events, however, can be challenging, and current imaging techniques are limited in their ability to detect early atherosclerosis. Coronary endothelial dysfunction can be considered a marker for early atherosclerosis 1 and has been shown to be associated with an increased risk of ischemic cardiac events and stroke. [2][3][4][5][6] A systemic biomarker that is an independent predictor of coronary endothelial dysfunction would be valuable in identifying patients in the early stages of coronary atherosclerosis and those who are at risk for future cardiac events.8Ϯ73 See page 5Four population-based studies have shown that elevated lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) levels are associated with an increased risk of coronary heart disease and ischemic stroke. 7-10 Lp-PLA 2 is a member of the phospholipase A 2 family of enzymes and is a 45.4-kDa protein produced by macrophages, T lymphocytes, and mast cells. 11,12 Approximately 80% of Lp-PLA 2 circulates bound to low-density lipoprotein (LDL), whereas the other 20% is bound to high-density lipoprotein (HDL). 13,14 Lp-PLA 2 hydrolyzes the sn2 ester bond in phospholipids of which the fatty acid moiety has been shortened or altered by oxidation to yield oxidized fatty acid and lysophosphatidylcholine. 15 These metabolites have proinflammatory properties, 16 and lysophosphatidylcholine has been shown to have adverse effects on endothelial function. [17][18][19] Lp-PLA 2 could, therefore, play a direct role in the development of endothelial dysfunction and coronary artery disease. In addition, it may also serve as a useful biomarker for predicting coronary endothelial dysfunction.The current study was performed to test the hypothesis that Lp-PLA 2 is associated with coronary endothelial dysfunction and is an independent predictor of endothelial dysfunction. MethodsThe study was approved by the Institutional Review Board at the Mayo Clinic. Written informed consent was obtained from patients Ն18 years of age undergoing coronary angiography and coronary endothelial function asse...

Two a-amino acids, 3-phosphono-2-aminopropionic and 4-phosphono-2-aminobutyric, are used to link zinc atoms in three-dimensional structures where the three phosphonic and one of the carboxylic oxygen atoms coordinate to the metal, while the protonated amino groups and the second carboxylic oxygen atom are not coordinated and remain terminal in the voids of the framework.

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Objective-The association between cholesterol and endothelial dysfunction remains controversial. We tested the hypothesis that lipoprotein subclasses are associated with coronary endothelial dysfunction.Methods and Results-Coronary endothelial function was assessed in 490 patients between November 1993 and February 2007. Fasting lipids and nuclear magnetic resonance (NMR) lipoprotein particle subclasses were measured. There were 325 females and 165 males with a mean age of 49.8±11.6 years. Coronary endothelial dysfunction (epicardial constriction >20% or increase in coronary blood flow <50% in response to intracoronary acetylcholine) was diagnosed in 273 patients, the majority of whom (64.5%) had microvascular dysfunction. Total cholesterol and LDL-C (low density lipoprotein cholesterol) were not associated with endothelial dysfunction. One-way analysis and multivariate methods adjusting for age, gender, diabetes, hypertension and lipidlowering agent use were used to determine the correlation between lipoprotein subclasses and coronary endothelial dysfunction. Epicardial endothelial dysfunction was significantly correlated with total (p = 0.03) and small LDLp (LDL particles) (p<0.01) and inversely correlated with total and large HDLp (high density lipoprotein particles) (p <0.01).Conclusions-Epicardial, but not microvascular, coronary endothelial dysfunction was associated directly with LDL particles and inversely with HDL particles, suggesting location-dependent impact of lipoprotein particles on the coronary circulation.

BACKGROUND:We evaluated the sensitivity, precision, and concordance of 4 assays designed to detect aspirin responsiveness or resistance.