Clinical aspects of plasma platelet-activating factor-acetylhydrolase.
Plasma platelet-activating factor (PAF)-acetylhydrolase (PAF-AH), which is characterized by tight association with plasma lipoproteins, degrades not only PAF but also phospholipids with oxidatively modified short fatty acyl chain esterified at the sn-2 position. Production and accumulation of these phospholipids are associated with the onset of inflammatory diseases and preventive role of this enzyme has been evidenced by many recent studies including prevalence of the genetic deficiency of the enzyme in the patients and therapeutic effects of treatment with recombinant protein or gene transfer. With respect to the atherosclerosis, however, it is not fully cleared whether this enzyme plays an anti-atherogenic role or pro-atherogenic role because plasma PAF-AH also might produce lysophosphatidylcholine (LysoPC) and oxidatively modified nonesterified fatty acids with potent pro-inflammatory and pro-atherogenic bioactivities. These dual roles of plasma PAF-AH might be regulated by the altered distribution of the enzyme between low density lipoprotein (LDL) and high density lipoprotein (HDL) particles because HDL-associated enzymes are considered to contribute to the protection of LDL from oxidative modification. This review focuses on the recent findings which address the role of this enzyme in the human diseases especially including asthma, septic shock and atherosclerosis.
Karasawa
Ken
K
Laboratory of Molecular Pharmaceutics, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa 199-0195, Japan. karasawa@pharm.teikyo-u.ac.jp
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood* / Q000172:deficiency / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008244:Lysophosphatidylcholines / Q000097:blood; D010084:Oxidation-Reduction / Q000187:drug effects; D011994:Recombinant Proteins / Q000097:blood / Q000627:therapeutic use; D012772:Shock, Septic / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D005227:Fatty Acids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D011994:Recombinant Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase