Atorvastatin preferentially reduces LDL-associated platelet-activating factor acetylhydrolase activity in dyslipidemias of type IIA and type IIB.
Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A(2) that is primarily associated with low density lipoprotein (LDL). PAF-AH activity has also been found in high density lipoprotein (HDL), although it has recently been indicated that there is no PAF-AH protein in HDL. Plasma paraoxonase 1 (PON1) is an HDL-associated esterase, which also exhibits PAF-AH-like activity. The effect of atorvastatin (20 mg per day for 4 months) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA (n=55) or type IIB (n=21) was studied. In both patient groups, atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions (LDL-4 and LDL-5). Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group. However, because of the reduction in LDL cholesterol levels, the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration. The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin.
Tsimihodimos
Vasilis
V
Department of Internal Medicine, University of Ioannina, Ioannina, Greece.
Karabina
Sonia-Athena P
SA
Tambaki
Afroditi P
AP
Bairaktari
Eleni
E
Goudevenos
John A
JA
Chapman
M John
MJ
Elisaf
Moses
M
Tselepis
Alexandros D
AD
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood; D043303:Aryldialkylphosphatase; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000378:metabolism; D004950:Esterases / Q000097:blood; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood*; D008264:Macrophages / Q000378:metabolism; D010741:Phospholipases A / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; D011758:Pyrroles; D000069059:Atorvastatin; D004950:Esterases; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human