Abstract 15071: Lipid Transfer to HDL in Patients With Coronary Artery Disease
Background: Systematic assessment of metabolic and functional aspects of HDL is important for the understanding of HDL anti-atherogenic role and the establishment of new coronary artery disease (CAD) markers and therapeutic goals. Lipid transfer between HDL and the other lipoproteins, a process mediated by CETP and PLTP, is a crucial step in HDL metabolism and determinant for HDL functions in cholesterol esterification and reverse cholesterol transfer.
Objective: Investigate whether development of CAD is associated with alterations in lipid transfers to HDL and in content of free cholesterol in the plasma and in HDL.
Methods: We studied 150 patients (79 with CAD and 71 without CAD (n-CAD)). Demographic, clinical, and laboratory data were similar for both groups. Fasting plasma samples were incubated for 1h at 37oC with a donor artificial nanoemulsion labeled with 3H -cholesteryl-esters and 14C -phospholipids or 14C- free-cholesterol and 3H -triglycerides. Radioactive lipids transferred from the donor nanoemulsion to HDL were quantified in the supernatant after chemical precipitation of non-HDL fractions and nanoemulsion.
Results: In CAD group, total cholesterol, LDL-cholesterol, triglycerides and apoB were higher than in n-CAD. CAD showed diminished transfer to HDL of free-cholesterol (CAD=6.9 ± 1.3; n-CAD= 8.3 ± 1.5%, p<0.0001), triglycerides (4.4 ± 0.8 vs 5.0 ±0.6%, p<0,0001), and phospholipid (21.2 ± 3.1 vs 25.7 ± 1.8%, p<0.0001), whereas the transfer of cholesteryl-ester was higher (5.0 ± 1.0 vs 4.3 ± 0.9%, p<0.0001). Plasma free-cholesterol was higher in CAD (CAD=36.8 ± 8.1; n-CAD=34.4 ± 7.1, p=0.04),while the content of free-cholesterol in HDL was smaller (7.6 ± 2.4 vs 8.8 ± 2.9, p<001) . HDL particle diameter was higher in CAD (8.5 ± 0.5; 8.2 ± 0.4; p <0.0001) as well as CETP concentration (3.5 ± 0.7 vs 3.0 ± 1.0, p=0.003).
Conclusion: The reduction of free-cholesterol transfer to HDL may impair cholesterol esterification and reverse cholesterol transport. Alterations in triglyceride and cholesteryl-ester transfer may affect lipoprotein stability. Those disturbances in HDL metabolism may facilitate the emergence of CAD.
- © 2013 by American Heart Association, Inc.