Cardiology Department and Molecular Immunology Laboratory, Onassis Cardiac Surgery Center, Athens, Greece.
Lipids Health Dis. 2012 Jul 8;11:89. doi: 10.1186/1476-511X-11-89.
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.
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.
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.
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.
Tangier 病（TD）是一种罕见的家族综合征的表型表达，其突变发生在 ABCA1 转运体上。TD 患者患冠状动脉疾病的风险是可变的。另一方面，血小板激活因子（PAF）介质在动脉粥样硬化中的关键作用已经被发现。血浆脂蛋白是细胞中 PAF 乙酰水解酶（PAF-AH）的载体，在血浆中称为脂蛋白-磷脂酶 A2（Lp-PLA2），是血液中 PAF 水平的调节剂。此外，PAF 可以从重塑和从头合成途径生物合成，其中溶血小板激活因子乙酰转移酶（Lyso-PAF-AT）和血小板激活因子胆碱磷酸转移酶（PAF-CPT）是调节酶。本研究的目的是在具有独特突变（C2033A）的 TD 患者中研究血液中 PAF 的浓度、富含血小板的血浆（PRP）对 PAF、二磷酸腺苷（ADP）和凝血酶的 50%聚集等效浓度（EC50）值，以及 PAF 代谢酶 Lp-PLA2、PAF-AH、Lyso-PAF-AT 和 PAF-CPT 的活性。
通过聚集仪测量 PRP 的 EC50 值。在体外酶促测定后，通过色谱分离和在生物测定中测量产生的 PAF，确定 PAF-CPT 和 Lyso-PAF-AT 的比活性。在体外酶促测定后，通过放射性 PAF 的衰减来测定 PAF-AH 和 Lp-PLA2 的比活性。
与健康女性相比，TD 患者血液中的结合 PAF 值较低，PAF-CPT 和 Lyso-PAF-AT 的比活性降低，血小板和白细胞中的 PAF-AH 比活性以及血浆中的 Lp-PLA2 活性增加，PAF 和凝血酶的 EC50 较高。
Lp-PLA2 活性增加，以及 PAF-CPT 和 Lyso-PAF-AT 的活性降低，解释了 TD 患者结合 PAF 水平降低和 PAF 的 EC50。然而，总 PAF 处于正常范围内，这可能是 TD 患者没有 CAD 的原因之一。
