TRANSFER OF PHOSPHOLIPASE-A-RESISTANT PYRENE-DIALKYL-GLYCEROPHOSPHOCHOLINE TO PLASMA-LIPOPROTEINS - DIFFERENCES BETWEEN LP[A] AND LDL

cyl-2-O-pyrenedecanyl-sn-glycero-3-phosphocholine, a non-hydrolyzable fluorescent diether analog of phosphatidylcholine (PC), was synthesize d as a probe for studying phospholipid transfer to different lipoprote in classes with potential phospholipase activities. After incubation o f total human plasma with the new probe at 37 degrees C for 4.5 h, a c haracteristic partition between the main lipoprotein fractions was obs erved. The fluorescent lipid was not degraded under these conditions a nd, therefore, served as a measure for choline glycerophospholipid dis tribution between plasma lipoproteins. In low density lipoprotein (LDL ) and high density lipoprotein-3 (HDL(3)) the fluorescent PC analog sh owed only monomer fluorescence, whereas in Lp[a] and HDL(2) monomer an d excimer fluorescence were observed, indicating that the fluorescent phosphatidylcholine analog was incorporated into the respective lipopr oteins to a different extent. According to the increased pyrene excime r fluorescence in Lp[a] compared with LDL the labeled phosphatidylchol ine must be enriched and/or clustered in Lp[a]. Data from phospholipid and total fluorescence analyses are compatible with the assumption of higher label concentration in Lp[a]. On the other hand, transfer rate s for serum protein catalyzed lipid transport into isolated Lp[a] were slower as compared to LDL. It is suggested that slower lipid transfer to Lp[a] under these conditions is due to the decreased lipid mobilit y in the Lp[a] surface, whereas the higher extent of label partition i nto Lp[a] as observed in total plasma might be due to the higher affin ity of apolipoproteins for phosphatidylcholine in Lp[a] (Sommer, A., e t a]. 1992. J. Biol. Chem. 267: 24217-24222). The use of a fluorescent dialkyl- instead of diacyl-glycerophosphocholine for transfer studies was mandatory, as we found that lipoproteins contained phospholipase A(2) activity toward long-chain phosphatidylcholine. The lipoprotein-a ssociated phospholipase A(2) was three times more active in Lp[a] than in LDL. The degradation products formed by the phospholipase, fatty a cids, and lyse-PC may add to the high atherogenic potential of Lp[a].