PROTEIN GLYCOSYLATION AND THE PATHOGENESIS OF ATHEROSCLEROSIS
PROTEIN GLYCOSYLATION AND THE PATHOGENESIS OF ATHEROSCLEROSIS
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DOI：
10.1016/s0026-0495(85)80008-1
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发表时间：
1985-01-01
影响因子：
9.8
通讯作者：
BROWNLEE, M
中科院分区：
文献类型：
--
作者：
CERAMI, A;VLASSARA, H;BROWNLEE, M
本文综述了非酶糖基化的研究进展，这是潜在的相关动脉粥样硬化和相关的知识，通过一个假设模型的基础上，动脉粥样硬化发生的糖尿病患者观察到的加速大血管疾病。最近获得了关于复杂糖基化加合物的重要新信息，这些加合物通过一系列进一步的反应和重排从最初的Amadori产物非常缓慢地形成。这些加合物称为高级糖基化终产物（AGE），不像Amadori产物那样可逆。因此，它们继续无限期地积累在长寿命的分子上，如胶原蛋白和核酸。AGE共价捕获可溶性血浆蛋白，作为巨噬细胞识别和摄取的信号，并诱导双链质粒DNA的突变。AGE对胶原蛋白上的低密度脂蛋白的共价捕获可能促进糖尿病患者动脉壁中的过度脂质积聚，而AGE对血管性血友病因子的捕获可能增加血小板粘附和聚集，导致动脉内膜中的平滑肌细胞增殖。通过清除巨噬细胞识别和摄取AGE-蛋白衍生物可能通过刺激巨噬细胞分泌产物如巨噬细胞衍生生长因子的释放而进一步促进动脉粥样硬化形成的过程。AGE在平滑肌细胞DNA上的积累也可能通过增加影响生长控制的突变率来增强动脉平滑肌细胞的增殖。
This review summarizes the progress of research in nonenzymatic glycosylation that is of potential relevance to atherosclerosis and relates this knowledge to the accelerated large-vessel disease observed in diabetics through a hypothetical model based on current concepts of atherogenesis. Critical new information has recently been obtained about complex glycosylation adducts, which form very slowly through a series of further reactions and rearrangements from the initial Amadori product. These adducts, called advanced glycosylation end products (AGE), are not reversible like the Amadori product. Thus, they continue to accumulate indefinitely on long-lived molecules such as collagen and nucleic acids. AGE covalently trap soluble plasma proteins, act as signals for macrophage recognition and uptake, and induce mutations in double-stranded plasmid DNA. Covalent trapping of low-density lipoproteins by AGE on collagen may promote excessive lipid accumulation in the arterial walls of diabetics, whereas trapping of von Willebrand factor by AGE may increase platelet adhesion and aggregation, leading to smooth muscle cell proliferation in the arterial intima. Recognition and uptake of AGE-protein derivatives by scavenging macrophages may further contribute to the process of atherogenesis by stimulating the release of such macrophage secretory products as macrophage-derived growth factor. Accumulation of AGE on smooth muscle cell DNA may also enhance proliferation of arterial smooth muscle cells by increasing the rate of mutations that affect growth control.