title: Platelet-activating factor acetylhydrolase: is it good or bad for you?
abstract: OBJECTIVE
  Although findings obtained from various studies are inconclusive in determining whether plasma platelet-activating factor acetylhydrolase, or lipoprotein-associated phospholipase A2, plays a proatherogenic or antiatherogenic role in atherosclerosis, many recent reviews appear to favor it as a risk factor for coronary artery disease. To provide a contrasting view, this review focuses on the enzyme's antiatherogenic and antiinflammatory properties.
  
  
  RESULTS
  A recent report demonstrates that plasma platelet-activating factor acetylhydrolase activity increases in men and women with stable angina or acute coronary syndromes, supporting previously published data that plasma levels of the protein are independently and positively associated with the risk of coronary artery disease. In contrast, at least four lines of evidence indicate that the enzyme has strong antiatherogenic properties: (1) it inhibits the effects of LDL oxidation, (2) genetic deficiency of plasma levels constitutes a risk factor for vascular diseases including atherosclerosis, (3) adenoviral transfer of the protein reduces atherosclerosis in apolipoprotein E-deficient mice, and (4) pretreatment of an electronegative LDL subfraction isolated from hypercholesterolemic human plasma with a recombinant platelet-activating factor acetylhydrolase completely abolishes the proapoptotic effects of the electronegative LDL on vascular endothelial cells. Additionally, treatment with the recombinant product reduced mortality from severe sepsis in a phase IIb clinical trial. In an animal study, transfection of tumor cells with platelet-activating factor acetylhydrolase inhibited tumor growth at the site of implantation.
  
  
  CONCLUSIONS
  Plasma platelet-activating factor acetylhydrolase becomes progressively activated as atherosclerosis progresses, but lines of evidence indicate that the enzyme possesses potent antiatherogenic and antiinflammatory properties. This raises the question of whether increased activity is a cause or a result of atherosclerosis and, consequently, whether inhibiting the enzyme's activities may decelerate or accelerate the progress of the disease.
authors.affiliation: Department of Medicine, Section of Atherosclerosis and Lipoprotein Research, Baylor College of Medicine, 6565 Fannin, Mail Station A-601, Houston, TX 77030, USA. cchen@bcm.tmc.edu
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D018384:Oxidative Stress; D054467:Phospholipases A2
chemical_list: D008077:Lipoproteins, LDL; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase