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Journal of Lipid Research, Vol. 43, 307-315, February 2002
Copyright © 2002 by Lipid Research, Inc.

Increased formation of lysophosphatidic acids by lysophospholipase D in serum of hypercholesterolemic rabbits

Correspondence to: Akira Tokumura, To whom correspondence should be addressed., tokumura{at}ph.tokushima-u.ac.jp (E-mail)

Lysophosphatidic acid (LPA) is a biologically active phospholipid that has been identified as a vasoactive principle in incubated plasma and serum of mammals. Previously, we found that mammalian plasma and serum contain a lysophospholipase D, which hydrolyzes lysophosphatidylcholines (LPCs) with different fatty acyl groups to the corresponding LPAs during its incubation at 37°C. In this study, we examined whether lysophospholipase D activity and levels of LPCs in rabbit serum were modulated by feeding rabbits a high cholesterol diet. Results showed that the serum levels of LPCs increased gradually in animals fed a high cholesterol diet for 12 weeks. We found that the levels of individual LPAs formed on incubation of serum for 24 h increased with an increase in the period of feeding of rabbits a high cholesterol diet. LPA with a linoleate residue was the most abundant LPA, followed in order by 16:0-, 18:1- and 18:0-LPAs. LPA was found to increase attachment of the monocytic cell line THP-1 to vascular endothelial cells pre-stimulated with tumor necrosis factor-.

These results indicated that increases in the levels of LPAs generated by lysophospholipase D in the blood of hypercholesterolemic rabbits may be relevant to attachment of monocytes to vascular walls, a key phenomenon observed at an early stage of atherosclerosis. — Tokumura, A., Y. Kanaya, M. Kitahara, M. Miyake, Y. Yoshioka, and K. Fukuzawa. Increased formation of lysophosphatidic acids by lysophospholipase D in serum of hypercholesterolemic rabbits. J. Lipid Res. 2002. 43: 307–315.

Supplementary key words: lysophosphatidylcholine, phosphatidylcholine, vascular endothelial cell, atherosclerosis, gas chromatography-mass spectrometry

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