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 A 2 (Lp-PLA 2 ) 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 (EC 50 ) values of platelet rich plasma (PRP) toward PAF, adenosine diphosphate (ADP) and thrombin, and the activities of PAF metabolic enzymes Lp-PLA 2 , PAF-AH, Lyso-PAF-AT and PAF-CPT. Methods The EC 50 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-PLA 2 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-PLA 2 activity in plasma compared to healthy women. The EC 50 of PAF and Thrombin were higher compared to healthy women. Conclusion The increased Lp-PLA 2 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 EC 50 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.

In vivo effect of two first-line ART regimens on inflammatory mediators in male HIV patients

“…The isolations of plasma, platelets (HPs) and leukocytes (HLs) were carried out as previously described [ 40 ]. Briefly, human blood was collected from an antecubital vein and distributed into a polyethylene tube containing anticoagulant in a ratio of blood/anticoagulant: 9/1, in a total volume of 10 mL.…”

“…Dithiothreitol-insensitive PAF-CPT and lyso-PAF-AT activity assays were performed on the homogenates of leukocytes and platelets. PAF-AH activity assays were performed on the homogenates of leukocytes and platelets as well as Lp-PLA2 activity assays on plasma as previously described [ 40 ]. The enzyme activity is expressed as pmol/min/mg of total protein or pmol/min/μL of plasma.…”