Makita Z, Yanagisawa K, Kuwajima S, Bucala R, Vlassara H, Koike T
Hokkaido University, School of Medicine, Sapporo, Japan.
Nephrol Dial Transplant. 1996;11 Suppl 5:31-3. doi: 10.1093/ndt/11.supp5.31.
Coronary artery disease and cerebrovascular disease due to the rapid progression of atherosclerosis is the principal cause of death in diabetes mellitus. Modification of low-density lipoproteins (LDL) by advanced glycosylation end-products (AGE) may play a central role in the development of atherosclerosis, especially in diabetic patients. An AGE-modified form of LDL (AGE-LDL) has been found to circulate in human plasma, and AGE modifications have been identified as being present on both the apoprotein (ApoB) and the phospholipid components of LDL. By utilizing an AGE-specific ELISA, we measured the AGE attached to the ApoB and lipid components of LDL from normal controls and diabetic patients with or without end-stage renal disease (ESRD), as well as lipid oxidation. AGE-ApoB, AGE-lipid and oxidized LDL (Ox-LDL) in diabetic patients were significantly higher than those in patients without diabetes. The correlation between AGE-ApoB and AGE-lipid were highly significant. An especially marked elevation of AGE-LDL was found in diabetic patients with ESRD. The correlation between the serum total cholesterol and the AGE-LDL (AGE-ApoB and AGE-lipid) was significant. In addition, based on the known biological properties of AGE-modified peptide (AGE-peptide), we have proposed that these chemically reactive circulating AGE-peptides contribute to tissue injury by reattaching to susceptible target proteins both within and outside the vasculature, and that this process accelerates vascular pathology in diabetic patients. These data indicate that AGE-modified LDLs may represent a particularly atherogenic form of LDL, and AGE-LDLs as well as AGE-peptides are likely to contribute to the development of atherosclerosis in diabetic patients.
动脉粥样硬化快速进展所致的冠状动脉疾病和脑血管疾病是糖尿病患者的主要死因。晚期糖基化终产物（AGE）对低密度脂蛋白（LDL）的修饰可能在动脉粥样硬化的发展中起核心作用，尤其是在糖尿病患者中。已发现一种AGE修饰形式的LDL（AGE-LDL）在人体血浆中循环，并且已确定AGE修饰存在于LDL的载脂蛋白（ApoB）和磷脂成分上。通过使用一种AGE特异性酶联免疫吸附测定法（ELISA），我们测量了来自正常对照以及患有或未患有终末期肾病（ESRD）的糖尿病患者的LDL的ApoB和脂质成分上附着的AGE，以及脂质氧化情况。糖尿病患者中的AGE-ApoB、AGE-脂质和氧化LDL（Ox-LDL）显著高于非糖尿病患者。AGE-ApoB与AGE-脂质之间的相关性非常显著。在患有ESRD的糖尿病患者中发现AGE-LDL有特别明显的升高。血清总胆固醇与AGE-LDL（AGE-ApoB和AGE-脂质）之间存在显著相关性。此外，基于AGE修饰肽（AGE-肽）已知的生物学特性，我们提出这些具有化学反应性的循环AGE-肽通过重新附着于血管系统内外的易感靶蛋白而导致组织损伤，并且这一过程加速了糖尿病患者的血管病变。这些数据表明，AGE修饰的LDL可能代表一种特别具有致动脉粥样硬化性的LDL形式，并且AGE-LDL以及AGE-肽可能促成糖尿病患者动脉粥样硬化的发展。
