Increased formation of lysophosphatidic acids by lysophospholipase D in serum of hypercholesterolemic rabbits.
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 degree 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-alpha. 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
Akira
A
Faculty of Pharmaceutical Sciences, The University of Tokushima, Shomachi, Tokushima 770-8505, Japan. tokumura@ph.tokushima-u.ac.jp
Kanaya
Yumi
Y
Kitahara
Masaki
M
Miyake
Maki
M
Yoshioka
Yasuko
Y
Fukuzawa
Kenji
K
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006937:Hypercholesterolemia / Q000097:blood* / Q000139:chemically induced; D008244:Lysophosphatidylcholines / Q000097:blood*; D008246:Lysophospholipids / Q000097:blood* / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases / Q000097:blood*; D011817:Rabbits; D000099189:Lysophospholipase D
D002791:Cholesterol, Dietary; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D