Oxidative modification of low density lipoprotein in normal and hyperlipidemic patients: effect of lysophosphatidylcholine composition on vascular relaxation

The elevated level of plasma low density lipopro- tein (LDL) in hyperlipidemic patients is an important risk fac- tor for the production of atherosclerosis. Plasma LDL must be modified before it can produce an impairment of endothe- liumdependent relaxation in aortic rings or enhancement of uptake by macrophages. The dramatic increase in lysophos- phatidylcholine (IysoPC) content in oxidatively modified LDL has been touted as an important biochemical factor for the impairment of endotheliumdependent relaxation. The pres- ent study was designed to examine the IysoPC composition of oxidized LDL samples from normal and hyperlipidemic sub- jects, and their effects on the impairment of endothelium-de- pendent relaxation. Oxidatively modified LDL from hyperlip- idemic patients contained a slightly higher level (17%) of IysoPC, but produced a disproportionately greater impair- ment of endothelium-dependent relaxation than that from normal subjects. As lysoPC is composed of many molecular species, its composition in oxidized LDL samples was ana- lyzed. In hyperlipidemic patients, lysoPC samples were found to contain a higher proportion of long-chain acyl groups. Sub- sequent studies revealed that only long-chain lysoPC (C,,,,,) were effective in impairing endothelium-dependent relax- ation. Experimental loading of oxidized LDL from normal subjects with long chain IysoPC to mimic levels observed in oxidized LDL from hyperlipidemic patients resulted in fur- ther impairment of' endothelium-dependent re1axation.M We conclude that the greater proportion of long-chain lysoPC found in the oxidized LDL of hyperlipidemic subjects is re- sponsible for the increased impairment of endothelium-de- pendent vascular relaxation. We propose that the high level of LDL found in the plasma of hyperlipidemic patient3, COLI- pled with its enhanced ability to generate long chain species of lysoPC during oxidative modification, are important factors for the development of atherosclerosis in these patients.- Chen, L., B. Liang, D. E. Froese, S. Liu, J. T. Wong, K. Tran, G. M. Hatch, D. Mymin, E. A. Kroeger, R. Y. K. Man, and P. C. Choy. Oxidative modification of low density lipoprotein in normal and hyperlipidemic patients: effect of lysophospha- tidylcholine composition on vascular relaxation. ,I. lipid B.5. 1997. 38: 546-553