Abstract 14551: LpPLA2 Activity and Mass Are Distributed Across Subfractions of Both LDL and HDL, and Relate Differently to CHD Progression
Objective: The current assumption is that the majority of the pro-oxidant enzyme Lipoprotein-Associated Phospholipase A2 (LpPLA2) resides on LDL-C, however the actual distribution of LpPLA2 on lipoproteins is unknown. We sought to determine the distribution of LpPLA2 mass and activity on different lipoproteins and the association with progression of coronary artery calcification (CAC).
Methods: From the Coronary Artery Calcification in Type 1 Diabetics (CACTI) study, we chose men with type 1 diabetes (not on statins, HDL-C in the 95th percentile by diabetes status) with and without CAC progression and matched controls (n=45). Lipoproteins were separated by Fast Protein Liquid Chromatography (FPLC). Individual samples of total plasma and pooled subfractions of LDL and HDL underwent LpPLA2 mass (PLAC) assays to measure accessible LpPLA2 mass on the surface of lipoprotein particles and activity (CAM) assays to measure total LpPLA2 activity dissociating from lipoprotein particles under denaturing conditions. All analyses were multivariate.
Results: Mean age was 39.9 ± 10.6 years, 44% diabetic, 56% with CAC progression. No significant associations were found between diabetes status and LpPLA2 mass or activity. Total LpPLA2 activity related to LDL-C and apo B (p=0.015 and p=0.001, respectively), and total LpPLA2 mass related to CAC progression (p=0.03). There was an inverse relationship between total LpPLA2 activity and HDL-C (p<0.001), but only a marginal association between total LpPLA2 mass and HDL-C (p=0.06). The amount of LpPLA2 activity and mass in pooled LDL sub-fractions related to LDL-C (p=0.01 and p=0.03), but not to diabetes or CAC progression. LpPLA2 mass and activity for pooled HDL had no relationship to lipids, diabetes, or CAC progression. Of interest, more LpPLA2 mass was found on HDL vs. LDL particles (54% vs 44%; p-value <0.001), while more LpPLA2 activity was in LDL vs. HDL particles (56% vs 40%; p-value = 0.02).
Summary and Conclusion: More LpPLA2 mass resides on HDL, but more LpPLA2 activity is associated with LDL. Total LpPLA2 activity had a strong inverse relationship to HDL-C, while total LpPLA2 mass was associated with CAC progression and LDL-C. These findings are novel, but more work is needed to determine their clinical significance.
- © 2010 by American Heart Association, Inc.