Cardiolipin is a normal component of human plasma lipoproteins
Cardiolipin is a normal component of human plasma lipoproteins
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DOI：
10.1073/pnas.97.4.1743
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发表时间：
2000-02-15
影响因子：
11.1
通讯作者：
Griffin, JH
中科院分区：
文献类型：
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作者：
Deguchi, H;Fernández, JA;Griffin, JH
抗心磷脂(抗CL)抗体诊断为抗磷脂抗体综合征，与静脉和动脉血栓形成的风险增加有关。由于CL选择性地增强纯化体系中激活的蛋白C/蛋白S依赖的抗凝血活性，而且CL不是一种正常的血浆成分，我们在血浆中寻找CL。用薄层层析、分析高效液相色谱(TLC)、分析高效液相色谱(HPLC法)对氯仿/甲醇(2：1，VOL/VOL)进行分析。纯化的A组分与对照CL(M：1448)无明显区别。用高效液相色谱法测定40例空腹血脂提取物(男20例，女20例)的CL时，CL(Mean+/-SD)为14.9+/-3.7mU/ml(9.1~24.2)，CL与磷脂酰丝氨酸(3.8+/-1.7mU/ml)无相关性。磷脂酰乙醇胺(+/-20微克/毫升)或含胆碱磷脂(1,580+/-280微克/毫升)。根据对空腹献血者的研究，CL(小于或等于94%)以极低密度脂蛋白(11+/-5.3%)、低密度脂蛋白(67+/-11.0%)和高密度脂蛋白(17+/-10%)的形式被回收，表明大多数CL(67%)是以低密度脂蛋白形式存在的。脂蛋白的相对磷脂含量分析表明，高密度脂蛋白选择性地富含CL和磷脂酰乙醇胺。这些结果表明CL是一种正常的血浆成分，提示抗磷脂抗体的表位可能包括CL或氧化性CL在脂蛋白中或与血浆蛋白(如β(2)-糖蛋白I、凝血酶原、蛋白C或S蛋白)或与血小板或内皮细胞表面蛋白的复合物中。
Anticardiolipin (anti-CL) antibodies, diagnostic for antiphospholipid antibody syndrome, are associated with increased risks of venous and arterial thrombosis. Because CL selectively enhances activated protein C/protein S-dependent anticoagulant activities in purified systems and because CL is not known to be a normal plasma component, we searched for CL in plasma. Plasma lipid extracts [chloroform/methanol (2:1, vol/vol)] were subjected to analyses by using TLC, analytical HPLC. and MS. A plasma lipid component was purified that was indistinguishable from reference CL (M:1448). When CL in 40 fasting plasma lipid extracts (20 males, 20 females) was quantitated by using HPLC, CL (mean +/- SD) was 14.9 +/- 3.7 mu g/ml (range 9.1 to 24.2) and CL was not correlated with phosphatidylserine (3.8 +/- 1.7 mu g/ml). phosphatidylethanolamine (64 +/- 20 mu g/ml), or choline-containing phospholipid (1,580 +/- 280 mu g/ml). Based on studies of fasting blood donors, CL (less than or equal to 94%) was recovered in very low density, low density, and high density lipoproteins (11 +/- 5.3%, 67 +/- 11.0%, and 17 +/- 10%, respectively), showing that the majority of plasma CL (67%) is in low density lipoprotein. Analysis of relative phospholipid contents of lipoproteins indicated that high density lipoprotein is selectively enriched in CL and phosphatidylethanolamine. These results shows that CL is a normal plasma component and suggest that the epitopes of antiphospholipid antibodies could include CL or oxidized CL in lipoproteins or in complexes with plasma proteins (e.g., beta(2)-glycoprotein I, prothrombin, protein C, or protein S) or with platelet or endothelial surface proteins.