Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism.
Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism.
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同型半胱氨酸和其他巯基化合物增强脂蛋白（a）与纤维蛋白的结合：血栓形成、动脉粥样硬化形成和巯基化合物代谢之间的潜在生化联系。
DOI：
10.1073/pnas.89.21.10193
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发表时间：
1992
影响因子：
11.1
通讯作者：
Borth,W
中科院分区：
文献类型：
--
作者：
Harpel,PC;Chang,VT;Borth,W
我们以前已经证明脂蛋白（a）[Lp（a）]，一种含有载脂蛋白（a）的致动脉粥样硬化脂蛋白，与纤溶酶原具有部分结构同源性，与纤溶酶修饰的纤维蛋白表面结合，我们假设这种相互作用可能是致动脉粥样硬化的。血液中同型半胱氨酸的中度升高是一种相对常见的疾病，易患过早的动脉粥样硬化。原因不明。我们现在报告，同型半胱氨酸，在浓度低至8 μ M，显着增加Lp（a）的纤维蛋白的亲和力。同型半胱氨酸诱导Lp（a）与纤溶酶处理的纤维蛋白之间的亲和力增加20倍，与未修饰的纤维蛋白之间的亲和力增加4倍。Lp（a）结合被ε-氨基己酸抑制，表明赖氨酸结合位点特异性。同型半胱氨酸不增强Lp（a）与其他表面结合蛋白的结合。半胱氨酸、谷胱甘肽和N-乙酰半胱氨酸也增加Lp（a）和纤维蛋白之间的亲和力。同型半胱氨酸不影响低密度脂蛋白或纤溶酶原与纤维蛋白的结合，也不改变Lp（a）的凝胶过滤洗脱模式。免疫印迹分析证明同型半胱氨酸部分降低Lp（a）。这些结果表明，同型半胱氨酸改变了完整的Lp（a）颗粒，从而增加了纤溶酶原样载脂蛋白（a）分子部分的反应性。巯基氨基酸增加Lp（a）与纤维蛋白结合的观察结果表明巯基化合物代谢、血栓形成和动脉粥样硬化形成之间存在生物化学关系。
We have previously shown that lipoprotein(a) [Lp(a)], an atherogenic lipoprotein that contains apolipoprotein(a), which shares partial structural homology to plasminogen, binds to a plasmin-modified fibrin surface, and we have postulated that this interaction may be atherogenic. Moderate elevations in blood homocysteine, a relatively common condition, predispose to premature atherosclerosis. The reasons for this are not established. We now report that homocysteine, at concentrations as low as 8 microM, significantly increases the affinity of Lp(a) for fibrin. Homocysteine induces a 20-fold increase in the affinity between Lp(a) and plasmin-treated fibrin and a 4-fold increase with unmodified fibrin. Lp(a) binding is inhibited by epsilon-aminocaproic acid, indicating lysine binding site specificity. Homocysteine does not enhance the binding of Lp(a) to other surface-bound proteins. Cysteine, glutathione, and N-acetylcysteine also increase the affinity between Lp(a) and fibrin. Homocysteine does not affect the binding of low density lipoprotein or plasminogen to fibrin, nor does it alter the gel-filtration elution pattern of Lp(a). Immunoblot analysis documents the fact that homocysteine partially reduces Lp(a). These results suggest that homocysteine alters the intact Lp(a) particle so as to increase the reactivity of the plasminogen-like apolipoprotein(a) portion of the molecule. The observation that sulfhydryl amino acids increase Lp(a) binding to fibrin suggests a biochemical relationship between sulfhydryl compound metabolism, thrombosis, and atherogenesis.