Cerami A, Vlassara H, Brownlee M
J Cell Biochem. 1986;30(2):111-20. doi: 10.1002/jcb.240300203.
This review summarizes progress in nonenzymatic glycosylation research of potential relevance to atherosclerosis using a hypothetical model based on current concepts of atherogenesis. Recently, new information has been presented showing that the initial Amadori product undergoes a series of further reactions and rearrangements to form adducts, called advanced glycosylation end products (AGE). These products are irreversible and accumulate indefinitely on long-lived molecules. These 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 lipoprotein (LDL) by AGE on collagen or elastin could promote lipid accumulation in the arterial wall, whereas AGE trapping of von Willebrand factor would increase platelet adhesion and aggregation leading to intimal smooth muscle cell proliferation. Recognition and uptake of AGE-proteins by scavenging macrophages could further contribute to the process of atherogenesis by stimulating release of macrophage secretory products such as macrophage-derived growth factor. Accumulation of AGE on smooth muscle cell DNA might also enhance arterial smooth muscle cell proliferation by increasing the rate of mutations affecting growth controls. This model should provide the basis for future experiments.
本综述利用基于当前动脉粥样硬化发生概念的假设模型，总结了与动脉粥样硬化潜在相关的非酶糖基化研究进展。最近，有新信息表明，最初的阿马多里产物会经历一系列进一步的反应和重排，形成称为晚期糖基化终产物（AGE）的加合物。这些产物是不可逆的，并在长寿命分子上无限期积累。这些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发生突变。AGE在胶原蛋白或弹性蛋白上对低密度脂蛋白（LDL）的共价捕获可促进脂质在动脉壁中的积累，而血管性血友病因子的AGE捕获会增加血小板黏附和聚集，导致内膜平滑肌细胞增殖。清除性巨噬细胞对AGE蛋白的识别和摄取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，进一步促进动脉粥样硬化的进程。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增殖。该模型应为未来的实验提供基础。
