Olkkonen Vesa M, Lehto Markku
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.
Ann Med. 2004;36(8):562-72. doi: 10.1080/07853890410018907.
Oxidized derivatives of cholesterol have been investigated actively for decades in the context of the oxidative hypothesis of atherosclerosis. Oxysterols arise in our tissues as a result of enzymatic or non-enzymatic oxidation reactions and are also obtained from dietary sources. Even though these compounds are found enriched in the atherosclerotic lesions in arterial walls, the plasma concentrations of oxysterols cannot, in the light of current knowledge, be regarded as a risk factor for atherosclerotic disease. However, oxysterols may still have important local effects in the arterial wall as factors that regulate the cellular lipid homeostasis and possibly the maturation of the lesions. Work during the past few years has revealed that oxysterols have a potential as signaling molecules that may play important roles in lipid metabolism, especially the reverse cholesterol transport process. This finding has recently moved oxysterols and the protein mediators of their biological effects, liver X receptors and cytosolic oxysterol binding proteins, into the center stage of atherosclerosis research.
在动脉粥样硬化的氧化假说背景下，胆固醇的氧化衍生物已被积极研究了数十年。氧化甾醇在我们的组织中通过酶促或非酶促氧化反应产生，也可从饮食来源获得。尽管这些化合物在动脉壁的动脉粥样硬化病变中含量丰富，但根据目前的知识，氧化甾醇的血浆浓度不能被视为动脉粥样硬化疾病的危险因素。然而，氧化甾醇作为调节细胞脂质稳态以及可能调节病变成熟的因素，仍可能在动脉壁中具有重要的局部作用。过去几年的研究表明，氧化甾醇具有作为信号分子的潜力，可能在脂质代谢，特别是逆向胆固醇转运过程中发挥重要作用。这一发现最近使氧化甾醇及其生物学效应的蛋白质介质——肝脏X受体和胞质氧化甾醇结合蛋白——成为动脉粥样硬化研究的核心。
