Platelet activating factor levels and metabolism in tangier disease: a case study

Lipids in Health and Disease

Constantinos A Demopoulos²  Genovefa Kolovou³  Marianna N Xanthopoulou¹  Sophia N Verouti²  George Stamatakis²  Vasiliki D Papakonstantinou²  Vana Kolovou² 

[1]Department of Science of Nutrition-Dietetics, Harokopio University, Athens, Greece

[2]Biochemistry Laboratory, Faculty of Chemistry, National and Kapodistrian University of Athens, Athens, Greece

[3]Cardiology Department and Molecular Immunology Laboratory, Onassis Cardiac Surgery Center, Athens, Greece

关键词: PAF-CPT;    Lyso-PAF-AT;    PAF-AH;    Lp-PLA₂;    Atherosclerosis;    Tangier Disease;    PAF;   

Others  :  1160252
DOI  :  10.1186/1476-511X-11-89

 received in 2012-05-14, accepted in 2012-06-25,  发布年份 2012

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2012 Kolovou et al.; licensee BioMed Central Ltd.

【 图 表 】

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