Role of lecithin-cholesterol acyltransferase in the metabolism of oxidizedphospholipids in plasma: studies with platelet-activating factor-acetyl hydrolase-deficient plasma

To determine the relative importance of platelet-activating factor-acetylhy drolase (PAF-AH) and lecithin-cholesterol acyltransferase (LCAT) in the hyd rolysis of oxidized phosphatidylcholines (OXPCs) to lyso-phosphatidylcholin e (lyso-PC), we studied the formation and metabolism of OXPCs in the plasma of normal and PAF-AH-deficient subjects. Whereas the loss of PC following oxidation was similar in the deficient and normal plasmas, the formation of lyse-PC was significantly lower, and the accumulation of OXPC was higher i n the deficient plasma. Isolated LDL from the PAF-AH-deficient subjects was more susceptible to oxidation, and stimulated adhesion molecule synthesis in endothelial cells, more than the normal LDL. Oxidation of 16:0-[1-C-14]- 18:2 PC, equilibrated with plasma PC, resulted in the accumulation of label ed short- and long-chain OXPCs, in addition to the labeled aqueous products . The formation of the aqueous products decreased by 80%, and the accumulat ion of short-chain OXPC increased by 110% in the deficient plasma, compared to the normal plasma showing that PAF-AH is predominantly involved in the hydrolysis of the truncated OXPCs. Labeled sn-2-acyl group from the long-ch ain OXPC was not only hydrolyzed to free fatty acid, but was preferentially transferred to diacylglycerol, in both the normal and deficient plasmas. I n contrast, the acyl group from unoxidized PC was transferred only to chole sterol, showing that the specificity of LCAT is altered by OXPC. It is conc luded that, while PAF-AH carries out the hydrolysis of mainly truncated OXP Cs, LCAT hydrolyzes and transesterifies the long-chain OXPCs. (C) 1999 Else vier Science B.V. All rights reserved.