Glycoxidation and lipoxidation in atherogenesis
Glycoxidation and lipoxidation in atherogenesis
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DOI：
10.1016/s0891-5849(00)00228-8
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发表时间：
2000-06-15
影响因子：
7.4
通讯作者：
Thorpe, SR
中科院分区：
文献类型：
--
作者：
Baynes, JW;Thorpe, SR
动脉粥样硬化可被视为一种年龄相关性疾病，由生物系统中的非酶化学反应引发。血管壁中脂蛋白中脂质的过氧化导致局部产生反应性羰基物质，其介导巨噬细胞的募集、细胞活化和增殖以及高级脂氧化终产物（ALE）对血管蛋白的化学修饰。ALE及其前体影响血管壁的结构和功能，为动脉粥样硬化形成奠定基础。糖尿病患者动脉粥样硬化的风险增加可能是由于碳水化合物产生额外的羰基和晚期糖基化终产物（AGEs）对蛋白质的额外化学修饰。动脉粥样硬化中反应性羰基前体增加以及由此产生的ALE和AGEs的可能来源是无法维持体内平衡和可氧化底物（脂质）单独增加，而不是氧化应激。亲核AGE抑制剂，如氨基胍和吡哆胺，其捕获反应性羰基并抑制糖尿病中AGE的形成，也捕获动脉粥样硬化中的生物活性脂质和ALE前体。这些药物应能有效延缓动脉粥样硬化的发展，即使在非糖尿病患者中也是如此。(C)2000 Elsevier Science Inc.
Atherosclerosis may be viewed as an age-related disease initiated by nonenzymatic, chemical reactions in a biological system. The peroxidation of lipids in lipoproteins in the vascular wall leads to local production of reactive carbonyl species that mediate recruitment of macrophages, cellular activation and proliferation, and chemical modification of vascular proteins by advanced lipoxidation end-products (ALEs). The ALEs and their precursors affect the structure and function of the vascular wall, setting the stage for atherogenesis. The increased risk for atherosclerosis in diabetes may result from additional carbonyl production from carbohydrates and additional chemical modification of proteins by advanced glycation end-products (AGEs). Failure to maintain homeostasis and the increase in oxidizable substrate (lipid) alone, rather than oxidative stress, is the Likely source of the increase in reactive carbonyl precursors and the resultant ALEs and AGEs in atherosclerosis. Nucleophilic AGE-inhibitors, such as aminoguanidine and pyridoxamine, which trap reactive carbonyls and inhibit the formation of AGEs in diabetes, also trap bioactive lipids and precursors of ALEs in atherosclerosis. These drugs should be effective in retarding the development of atherosclerosis, even in nondiabetic patients. (C) 2000 Elsevier Science Inc.