Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein.
Mildly oxidized low density lipoprotein (MM-LDL) produced by oxidative enzymes or cocultures of human artery wall cells induces endothelial cells to produce monocyte chemotactic protein-1 and to bind monocytes. HDL prevents the formation of MM-LDL by cocultures of artery wall cells. Using albumin treatment and HPLC we have isolated and partially characterized bioactive oxidized phospholipids in MM-LDL. Platelet activating factor-acetylhydrolase (PAF-AH), a serine esterase, hydrolyzes short chain acyl groups esterified to the sn-2 position of phospholipids such as PAF and particular oxidatively fragmented phospholipids. Treatment of MM-LDL with PAF-AH (2-4 x 10(-2) U/ml) eliminated the ability of MM-LDL to induce endothelial cells to bind monocytes. When HDL protected against the formation of MM-LDL by cocultures, lysophosphatidylcholine was detected in HDL; whereas when HDL was pretreated with diisopropyl fluorophosphate, HDL was no longer protective and lysophosphatidylcholine was undetectable. HPLC analysis also revealed that the active oxidized phospholipid species in MM-LDL had been destroyed after PAF-AH treatment. In addition, treatment of MM-LDL with albumin removed polar phospholipids that, when reisolated, induced monocyte binding to endothelial cells. These polar phospholipids, when treated with PAF-AH, lost biological activity and were no longer detected by HPLC. These results suggest that PAF-AH in HDL protects against the production and activity of MM-LDL by facilitating hydrolysis of active oxidized phospholipids to lysolipids, thereby destroying the biologically active lipids in MM-LDL.
Watson
A D
AD
Department of Pathology, University of California, Los Angeles 90024.
Navab
M
M
Hama
S Y
SY
Sevanian
A
A
Prescott
S M
SM
Stafforini
D M
DM
McIntyre
T M
TM
Du
B N
BN
Fogelman
A M
AM
Berliner
J A
JA
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001011:Aorta / Q000502:physiology; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000302:isolation & purification; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010741:Phospholipases A / Q000378:metabolism*; D010743:Phospholipids / Q000032:analysis / Q000302:isolation & purification; D011817:Rabbits; D012709:Serum Albumin / Q000494:pharmacology
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D012709:Serum Albumin; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase