Effect of hypolipidemic drugs on lipoprotein-associated platelet activating factor acetylhydrolase. Implication for atherosclerosis.
Human plasma platelet activating factor acetylhydrolase (PAF-AH) is an enzyme associated mainly with the apolipoprotein B (apoB)-containing lipoproteins and primarily with low-density lipoprotein (LDL). A small proportion of enzyme activity is also associated with high-density lipoprotein (HDL). PAF-AH activity is essential for the metabolism of PAF and oxidized phospholipids, i.e. bioactive lipids that are involved in the pathophysiology of atherosclerosis. Thus, PAF-AH may play a significant role in atherogenesis. Accumulating data indicate that PAF-AH associated with HDL particles plays a predominantly antiatherogenic role. By contrast, the role of LDL-associated PAF-AH remains controversial. Dyslipidemia induces a significant increase in total plasma PAF-AH activity and alters the enzyme distribution between proatherogenic apoB- and antiatherogenic apo AI-containing lipoproteins by increasing the PAF-AH activity associated with apoB-containing lipoproteins. The decreased rate of LDL removal from the circulation and the abnormal catabolism of triglyceride-rich lipoproteins play important roles in these abnormalities. Atorvastatin or fenofibrate therapy can restore, at least partially, the dyslipidemia-induced alterations in plasma PAF-AH by increasing the ratio of HDL-PAF-AH to plasma PAF-AH (or to LDL-cholesterol) levels, which may represent an important antiatherogenic effect of these hypolipidemic drugs.
Eisaf
Moses
M
Department of Internal Medicine, University of Ioannina, 45110 Ioannina, Greece.
Tselepis
Alexandros D
AD
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*
D000960:Hypolipidemic Agents; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase