Altered distribution of platelet-activating factor- acetylhydrolase activity between LDL and HDL as a function of the severity of hypercholesterolemia.
Platelet-activating factor-acetylhydrolase (PAF-AH) is a lipoprotein-associated phospholipase A2 capable of hydrolyzing platelet-activating factor (PAF) and oxidatively modified phospholipids. We studied the plasma- and lipoprotein-associated PAF-AH activity in patients with primary hypercholesterolemia. Thirty-eight unrelated patients with heterozygous familial hypercholesterolemia (HeteroFH), five patients with homozygous FH (HomoFH), and 33 patients with primary non-FH hypercholesterolemia (NonFH) participated in the study. In all patient groups the plasma PAF-AH activity was significantly elevated compared with 33 normolipidemic controls, the HomoFH having the highest and the NonFH patients showing the lowest enzyme activity. Gradient ultracentrifugation studies showed that this increase is not only due to the elevation in the plasma LDL but also to the increase in the PAF-AH activity associated with each LDL subfraction, being more profound in the small-dense LDL-5. Unlike LDL, no difference in the HDL-associated PAF-AH activity was observed among all groups. Consequently, an altered distribution of enzyme activity among apolipoprotein B (apoB)- and apolipoprotein A-I (apoA-I)-containing lipoproteins is observed in hypercholesterolemic patients, resulting in a significant decrease in the ratio of the HDL-associated PAF-AH to the total plasma enzyme activity compared with controls. This reduction is proportional to the increase of the plasma LDL-cholesterol (LDL-C) levels and consequently to the severity of the hypercholesterolemia. Thus, the ratio of HDL-associated PAF-AH-total plasma enzyme activity may be useful as a potential marker of atherogenicity in subjects with primary hypercholesterolemia.
Tsimihodimos
Vasilis
V
Department of Internal Medicine, University of Ioannina, 45110 Ioannina, Greece.
Karabina
Sonia-Athena P
SA
Tambaki
Afroditi P
AP
Bairaktari
Eleni
E
Miltiadous
George
G
Goudevenos
John A
JA
Cariolou
Marios A
MA
Chapman
M John
MJ
Tselepis
Alexandros D
AD
Elisaf
Moses
M
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000328:Adult; D001053:Apolipoproteins / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D008074:Lipoproteins / Q000097:blood / Q000145:classification / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A / Q000097:blood* / Q000378:metabolism; D054467:Phospholipases A2; D012720:Severity of Illness Index
D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase