Comparative analysis of lipid composition of normal and acute-phase high density lipoproteins

In the acute-phase response and in diseases with prolonged acute phases, no rmal HDL (NHDL) is converted into acute-phase HDL (APHDL) and becomes proin flammatory and unable to protect LDL against oxidative modification. Earlie r work had demonstrated that these changes are associated with alterations in apolipoprotein composition and enzymatic activity of APHDL, but the effe ct of the acute-phase condition on the lipid composition of APHDL had remai ned obscure. The present study shows marked quantitative differences in lip id composition between NHDL and APHDL. Specifically, APHDL contained 25% le ss total lipid per milligram of protein. Up to 50% of cholesteryl ester in the lipid core of APHDL was replaced by triacylglycerol; however, the total phospholipid/total neutral lipid ratios were the same as in NHDL, both lip oproteins giving similar calculated Lipid core radii. Furthermore, the phos phatidylcholine/sphingomyelin ratio in APHDL was nearly double that in NHDL , indicating a relative loss of sphingomyelin. A decrease was also seen in diacyl and alkenylacyl glycerophosphatidylethanolamine as well as in phosph atidylinositol of APHDL when compared with NHDL, APHDL contained proportion ally more saturated and less polyunsaturated and isoprostane-containing spe cies of phosphatidylcholine, as well as more saturated than unsaturated cho lesteryl esters. APHDL also contained significantly more free fatty acids, lysophosphatidylcholine, and free cholesterol. These changes in the lipid c omposition of HDL are consistent with the alterations in the apoprotein com position and enzymatic activity of APHDL and indicate proinflammatory and p roatherogenic roles for APHDL.