Munteanu Adelina, Zingg J-M, Azzi A
Institute of Biochemistry and Molecular Biology, University of Bern, Bern, Switzerland.
J Cell Mol Med. 2004 Jan-Mar;8(1):59-76. doi: 10.1111/j.1582-4934.2004.tb00260.x.
Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.
动脉粥样硬化及其并发症，如冠心病、心肌梗死和中风，是发达国家的主要死因。高血压、糖尿病、吸烟以及高胆固醇和高脂肪饮食显然会增加过早发生动脉粥样硬化的可能性，尽管其他因素，如个体基因组成，可能也起了额外作用。已经针对维生素E进行了多项流行病学研究和干预试验，其中一些研究表明它可以预防动脉粥样硬化。长期以来，人们认为维生素E通过减少低密度脂蛋白（LDL）氧化发挥作用，而LDL氧化是动脉粥样硬化起始的关键步骤。然而，在细胞水平上，维生素E通过抑制平滑肌细胞增殖、血小板聚集、单核细胞黏附、氧化型LDL摄取和细胞因子产生来发挥作用，所有这些反应都与动脉粥样硬化的进展有关。最近的研究表明，这些作用并非维生素E抗氧化活性的结果，而是该化合物精确分子作用的结果。据推测，维生素E与酶和蛋白质的特定相互作用是其非抗氧化作用的基础。维生素E会影响多种酶的活性（如蛋白激酶C、蛋白磷酸酶2A、环氧化酶-2、5-脂氧合酶、一氧化氮合酶、NADPH氧化酶、超氧化物歧化酶、磷脂酶A2），并调节与动脉粥样硬化相关的基因表达（如清道夫受体、整合素、选择素、细胞因子、细胞周期蛋白）。这些相互作用有望揭示维生素E的生物学特性，并有助于设计更好的策略来预防动脉粥样硬化进展。
