title: Platelet activating factor levels and metabolism in Tangier disease: a case study.
abstract: BACKGROUND
  Tangier disease (TD) is a phenotypic expression of rare familial syndrome with mutations in the ABCA1 transporter. The risk of coronary artery disease in patients with TD is variable. On the other hand the pivotal role of Platelet-Activating Factor (PAF) mediator in atheromatosis was found. Plasma lipoproteins are transporters of the PAF acetylhydrolase (PAF-AH) in cells and known as lipoprotein-phospholipase A2 (Lp-PLA2) in plasma and regulators of PAF levels in blood. In addition, PAF can be biosynthesized from the remodeling and the de novo pathways in which Lyso-platelet activating factor-acetyltransferase (Lyso-PAF-AT) and platelet activating factor-cholinephosphotransferase (PAF-CPT) are the regulatory enzymes. The aim of this study is to investigate in a TD patient with a unique mutation (C2033A), the concentration of PAF in blood, the Equivalent Concentration for 50% aggregation (EC50) values of platelet rich plasma (PRP) toward PAF, adenosine diphosphate (ADP) and thrombin, and the activities of PAF metabolic enzymes Lp-PLA2, PAF-AH, Lyso-PAF-AT and PAF-CPT.
  
  
  METHODS
  The EC50 value of PRP was measured by an aggregometer. The determination of the specific activity of PAF-CPT and Lyso-PAF-AT was made after in vitro enzymatic assay, chromatographic separation and measurement of the produced PAF in a biological assay with washed rabbit platelets. The determination of PAF-AH and Lp-PLA2 was made after an in vitro enzymatic assay from the decay of radioactive PAF.
  
  
  RESULTS
  The TD patient had lower bound-PAF values in blood, decreased specific activity of PAF-CPT and Lyso-PAF-AT, increased specific activity of PAF-AH in platelets and leukocytes and Lp-PLA2 activity in plasma compared to healthy women. The EC50 of PAF and Thrombin were higher compared to healthy women.
  
  
  CONCLUSIONS
  The increased Lp-PLA2 activity, as well as, the decreased activities of PAF-CPT and Lyso-PAF-AT, explain the decreased bound-PAF level in TD patient and the EC50 of PAF. However, total PAF is in a normal range and this probably can explain one of the reasons this TD patient has no CAD.
authors: Cardiology Department and Molecular Immunology Laboratory, Onassis Cardiac Surgery Center, Athens, Greece. bkolovou@gmail.com
authors: Vana
authors: V
authors: Kolovou
authors: Vasiliki D
authors: VD
authors: Papakonstantinou
authors: George
authors: G
authors: Stamatakis
authors: Sophia N
authors: SN
authors: Verouti
authors: Marianna N
authors: MN
authors: Xanthopoulou
authors: Genovefa
authors: G
authors: Kolovou
authors: Constantinos A
authors: CA
authors: Demopoulos
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000123:Acetyltransferases / Q000097:blood; D000244:Adenosine Diphosphate / Q000097:blood; D000328:Adult; D000368:Aged; D000818:Animals; D001681:Biological Assay; D001792:Blood Platelets / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology; D002798:Diacylglycerol Cholinephosphotransferase / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010972:Platelet Activating Factor / Q000378:metabolism*; D010974:Platelet Aggregation; D011817:Rabbits; D012016:Reference Values; D013631:Tangier Disease / Q000097:blood* / Q000150:complications / Q000235:genetics; D013917:Thrombin / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D010972:Platelet Activating Factor; D000244:Adenosine Diphosphate; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D002798:Diacylglycerol Cholinephosphotransferase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D013917:Thrombin