Brownlee M, Vlassara H, Cerami A
Diabetes. 1985 Sep;34(9):938-41. doi: 10.2337/diab.34.9.938.
Advanced nonenzymatic glycosylation products capable of cross-linking proteins accumulate on collagen in vivo in proportion to time-averaged blood glucose concentration. In this report, we have evaluated the ability of advanced nonenzymatic glycosylation products formed on collagen in vitro to covalently bind low-density lipoprotein (LDL) in a manner similar to that which occurs in human atherosclerotic lesions. At constant LDL concentration, covalent trapping increased linearly with the extent of advanced glycosylation product formation, from 1.42 +/- 0.15 to 4.46 +/- 0.36 micrograms LDL protein/mg collagen. At a constant level of collagen advanced glycosylation product, LDL binding increased as a function of increasing LDL concentration. At an LDL-cholesterol level of 103 mg/dl, covalent trapping of LDL by nonenzymatic glycosylation products on collagen averaged 3.2 times as much as control (P less than 0.01). These data indicate that LDL is bound specifically by reactive products generated by nonenzymatic glycosylation of collagen, and suggest that excessive LDL trapping by hyperglycemia-induced advanced glycosylation endproducts may contribute to the accelerated development of atherosclerosis in patients with diabetes mellitus.
能够使蛋白质发生交联的晚期非酶糖基化产物在体内胶原上的积累与时间平均血糖浓度成正比。在本报告中，我们评估了体外在胶原上形成的晚期非酶糖基化产物以类似于人类动脉粥样硬化病变中发生的方式共价结合低密度脂蛋白（LDL）的能力。在LDL浓度恒定的情况下，共价捕获随着晚期糖基化产物形成程度的增加而线性增加，从1.42±0.15微克LDL蛋白/毫克胶原增加到4.46±0.36微克LDL蛋白/毫克胶原。在胶原晚期糖基化产物水平恒定的情况下，LDL结合随着LDL浓度的增加而增加。在LDL胆固醇水平为103毫克/分升时，胶原上非酶糖基化产物对LDL的共价捕获平均是对照的3.2倍（P<0.01）。这些数据表明LDL被胶原非酶糖基化产生的反应性产物特异性结合，并提示高血糖诱导的晚期糖基化终产物过度捕获LDL可能有助于糖尿病患者动脉粥样硬化的加速发展。
