Abstract 441: Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) is Elevated in Acute Coronary Syndromes and Resides Predominantly in LDL
Lipoprotein associated phospholipase A2 (Lp-PLA2) may play a role in the formation of vulnerable atherosclerotic plaques and plaque rupture. Its plasma distribution and mass in subjects with acute coronary syndromes (ACS) are not characterized.
The objective of this study was to examine plasma levels and distribution of Lp-PLA2 in patient with ACS.
We compared plasma levels of LP-PLA2 in 23 patients within 48 hours of presentation of an ACS (visit 1) and 12 weeks after (visit 2), in 24 patients with chronic, stable coronary artery disease (sCAD) and in normal healthy controls. The distribution of Lp-PLA2 was determined by ultracentrifugation (UTC), high-performance liquid chromatography (HPLC), and polyethylene glycol (PEG) precipitation of plasma lipoproteins and immunoblotting analysis. Lp-PLA2 mass was determined by ELISA
The ACS patients (18 males/5 females, mean age 57±9.2) had hsCRP levels of 32.6±60.4 mg/L (ACS visit1) vs. 1.9±1.3 mg/L (ACS visit2), reflecting systemic inflammation. Stable CAD hsCRP 1.3±1.3 mg/L and controls 0.6±0.2 mg/L did not differ significantly. HDL cholesterol levels were 1.02±0.24 mmol/L for ACS visit 1, 1.00±0.3 mmol/L for ACS visit2, and 1.11±0.29 mmol/L for stable CAD. Plasma Lp-PLA2 levels were significantly higher in ACS visit1 subjects than in the ACS visit2 (144.3±60.6 vs. 89.5±40.0 ng/mL, p<0.0001). Interestingly, sCAD patients had slightly higher Lp-PLA2 levels that ACS visit 2 (p=0.003).
The distribution of Lp-PLA2 differed according to the technique used. We found that only approximately 45% of Lp-PLA2 mass remained in the lipoprotein fraction (d<1.21 g/L) after UTC, with the majority (43%) in the LDL fraction and only <3% in the HDL fraction. The remainder (55% was found in the d>1.21 g/L, suggesting that Lp-PLA2 is only loosely bound to lipoproteins, and the majority resides in LDL.
Here, we show that subjects with an ACS have markedly increased Lp-PLA2 levels acutely and that these levels fall within 12 weeks. Surprisingly, Lp-PLA2 is only loosely bound to lipoproteins and may be displaced in inflammatory conditions. The increase in Lp-PLA2 in ACS may contribute to the generation of oxidized fatty acyls and lysophopsphlipids and potentially compound the local inflammatory reaction.
- © 2013 by American Heart Association, Inc.