Abstract
BackgroundTangier 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.MethodsThe 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.ResultsThe 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.ConclusionThe 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.
Highlights
Tangier disease (TD) is a rare genetic disorder that was first described by Fredrickson et al [1] and it is characterized by nearly absence of high density lipoprotein (HDL) cholesterol in patients’ plasma
We measured Platelet-Activating Factor (PAF) levels in blood and we studied the Equivalent Concentration for 50% aggregation (EC50) values of PAF, thrombin and adenosine diphosphate (ADP) in Platelet-Rich Plasma (PRP)
Many studies expressed the PAF levels in pg/mL and for this reason we converted our results from fmol/mL to pg/mL
Summary
Tangier disease (TD) is a rare genetic disorder that was first described by Fredrickson et al [1] and it is characterized by nearly absence of high density lipoprotein (HDL) cholesterol in patients’ plasma. The inflammation is initiated by leukocytes and lipoproteins infiltration into the arterial wall (1), where the lipoproteins undergo oxidation (2) and the monocyte-derived macrophages after digestion of modified lipoprotein particles form foam cells [9]. Macrophages, after their activation, synthesize proinflammatory and prothrombotic factors such as platelet-activating factor (PAF) [10] which is a powerful mediator of inflammation [11] and a key factor for atherosclerosis [12]. 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
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