1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine and Coronary-Artery-Disease

The relationship between autoantibodies (autoAbs) to oxidized LDL (oxLDL) and coronary artery disease (CAD) remains controversial. IgM and IgG autoAbs to oxLDL and 1-palmitoyl-2 (5'-oxo-valeroyl)-sn-glycero-3-phosphorylcholine (POVPC), as well as the levels of non modified or modified ApoB-100 immune complexes (ICs), were measured in twenty patients undergoing clinically indicated coronary angiography, and in ten young healthy volunteer sera. The levels of IgM autoAbs to oxLDL did not differ between no CAD patients and healthy subjects, but the levels of these autoAbs were significantly higher in no CAD patients and healthy subjects in comparison with CAD patients. There was not difference in the levels of IgM anti-ApoB-100 ICs between both groups of patients. In contrast, the levels of ICs formed by IgM autoAbs and oxidative modified ApoB-100 were lower in patients with CAD than in patients without CAD. No differences were observed in the levels of autoAbs to POVPC among the groups. In conclusion, our results showed that the level of circulating oxLDL IgM autoAbs was lower in CAD patients than in no CAD patients, supporting the hypothesis that this kind of autoAbs might be inversely associated with the presence of atherosclerosis.

Topics: Adult; Aged; Apolipoprotein B-100; Autoantibodies; Cholesterol; Coronary Angiography; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Immunoglobulin M; Lipoproteins, LDL; Middle Aged; Phospholipid Ethers; Phospholipids; Receptors, Oxidized LDL; Triglycerides

We have developed a novel and rapid cell-free assay of the ability of HDL to prevent the formation of or inactivate oxidized phospholipids. HDL was tested for its ability to inhibit the oxidation of LDL, or inhibit the oxidation of l-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC) by hydroperoxyoctadecadienoic acid (HPODE), or inactivate oxidized PAPC (Ox-PAPC). In each case the fluorescent signal generated in the presence of the test substances and the test HDL was determined. As little as 2.5 microg of normal human HDL cholesterol significantly inhibited the fluorescent signal generated by Ox-PAPC; results did not differ regardless of whether the HDL was prepared by gel electrophoresis, fast protein liquid chromatography, or dextran sulfate precipitation. HDL from each of 27 patients with coronary atherosclerosis failed to inhibit the fluorescent signal generated by a control LDL, whereas HDL from each of 31 matched normal subjects with the same levels of HDL cholesterol significantly inhibited the signal. Results from an established cell-based assay (Navab, M., S. Hama, J. Cooke, G. M. Anantharamaiah, M. Chaddha, L. Jin, G. Subbanagounder, K. F. Faull, S. T. Reddy, N. E. Miller, and A. M. Fogelman. 2000. J. Lipid Res. 41: 1481-1494) were identical. HDL from the patients also failed to inhibit the fluorescent signal generated from PAPC plus HPODE (10 of 10 patients) whereas HDL from matched controls (8 of 8 patients) significantly inhibited the fluorescent signal. We conclude that this new assay has the potential to allow widespread testing of the hypothesis that HDL that is dysfunctional in preventing the formation or inactivating oxidized phospholipids may play an important role in the development of atherosclerosis.

Topics: Animals; Antioxidants; Aorta; Cell-Free System; Chemotaxis, Leukocyte; Clusterin; Coculture Techniques; Coronary Artery Disease; Endothelium, Vascular; Female; Fluoresceins; Fluorescent Dyes; Glycoproteins; Humans; Linoleic Acids; Lipid Peroxidation; Lipid Peroxides; Lipoproteins, HDL; Lipoproteins, LDL; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Molecular Chaperones; Monocytes; Muscle, Smooth, Vascular; Oxidation-Reduction; Phospholipid Ethers; Spectrometry, Fluorescence