Reduced PAF-acetylhydrolase activity associated with Lp(a) in patients with coronary artery disease.
Lipoprotein(a) [Lp(a)] may be an independent risk factor for coronary artery disease (CAD). Lp(a) is enriched in platelet activating factor acetylhydrolase (PAF-AH), an enzyme which hydrolyzes and inactivates platelet activating factor (PAF) and oxidized phospholipids that are implicated in atherogenesis. We determined the mass and catalytic properties of the Lp(a)-associated PAF-AH in 28 CAD patients in relation to the LDL-associated enzyme ones. Results were then compared to those of 30 control subjects and 16 unrelated patients with primary hypercholesterolemia (Type IIA dyslipidemia) before and after atorvastatin therapy. The mass, the specific activity and kinetic constants of the Lp(a)-associated PAF-AH were significantly lower in CAD patients compared to those of either controls or hypercholesterolemic patients, a phenomenon not observed for LDL-associated PAF-AH. The enzyme specific activity and kinetic constants were significantly increased after removal of apo(a) from Lp(a) by reductive cleavage, which was not found in the control population, suggesting that the apo(a) moiety of Lp(a) from CAD patients may play an important role in the observed lower catalytic efficiency of PAF-AH. The reduced PAF-AH mass and specific activity on Lp(a) is a feature characteristic of this lipoprotein in CAD patients and may lead to a diminished capability of Lp(a) to degrade proinflammatory phospholipids. The consequences of this phenomenon as regards the pathophysiological role of Lp(a) in atherosclerosis remain to be established.
Tsironis
Loukas D
LD
Laboratory of Biochemistry, Department of Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Katsouras
Christos S
CS
Lourida
Evangelia S
ES
Mitsios
John V
JV
Goudevenos
John
J
Elisaf
Moses
M
Tselepis
Alexandros D
AD
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000201:enzymology*; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase