Freedman J E, Farhat J H, Loscalzo J, Keaney J F
Whitaker Cardiovascular Institute, Boston University School of Medicine, MA 02118-2394, USA.
Circulation. 1996 Nov 15;94(10):2434-40. doi: 10.1161/01.cir.94.10.2434.
Epidemiological studies indicate that vitamin E (alpha-tocopherol) exerts a beneficial effect on cardiovascular disease. The effect of vitamin E has generally been attributed to its antioxidant activity and the antioxidant protection of LDL. Distinct from its effect on LDL, vitamin E is also known to inhibit platelet aggregation and adhesion in vitro, but the mechanism(s) responsible for these observations are not known.
Using gel-filtered platelets derived from platelet-rich plasma treated with alpha-tocopherol (500 mumol/L) or vehicle (0.5% ethanol), we found that inhibition of platelet aggregation by alpha-tocopherol was closely linked to its incorporation into platelets (r = -.78; P < .02). Platelet incorporation of alpha-tocopherol was associated with a significant reduction in platelet sensitivity to aggregation by adenosine 5'-diphosphate, arachidonic acid, and phorbol ester (PMA) by approximately, 0.15-, 2-, and 100-fold, respectively. In contrast, platelets treated similarly with butylated hydroxytoluene, another potent lipid-soluble antioxidant, did not demonstrate any change in sensitivity to these agents. Platelet incorporation of alpha-tocopherol inhibited PMA-induced stimulation of platelet protein kinase C (PKC) as determined by phosphorylation of the 47-kD PKC substrate. In 15 normal subjects, oral supplementation with alpha-tocopherol (400 to 1200 IU/d) resulted in an increase in platelet alpha-tocopherol content that correlated with marked inhibition of PMA-mediated platelet aggregation (r = .67; P < .01). Platelets derived from these subjects after supplementation also demonstrated apparent complete inhibition of PKC stimulation by PMA.
These data indicate that platelet incorporation of alpha-tocopherol at levels attained with oral supplementation is associated with inhibition of platelet aggregation through a PKC-dependent mechanism. These observations may represent one potential mechanism for the observed beneficial effect of alpha-tocopherol in preventing the development of coronary artery disease.
流行病学研究表明，维生素E（α-生育酚）对心血管疾病具有有益作用。维生素E的作用通常归因于其抗氧化活性以及对低密度脂蛋白（LDL）的抗氧化保护作用。与它对LDL的作用不同，维生素E在体外也已知可抑制血小板聚集和黏附，但其导致这些现象的机制尚不清楚。
使用用α-生育酚（500μmol/L）或赋形剂（0.5%乙醇）处理的富含血小板血浆来源的凝胶过滤血小板，我们发现α-生育酚对血小板聚集的抑制作用与其掺入血小板密切相关（r = -0.78；P < 0.02）。α-生育酚掺入血小板与血小板对5'-二磷酸腺苷、花生四烯酸和佛波酯（PMA）诱导的聚集敏感性显著降低相关，分别降低约0.15倍、2倍和100倍。相比之下，用另一种强效脂溶性抗氧化剂丁基羟基甲苯进行类似处理的血小板，对这些试剂的敏感性未显示任何变化。通过47-kD PKC底物的磷酸化测定，α-生育酚掺入血小板抑制了PMA诱导的血小板蛋白激酶C（PKC）的刺激。在15名正常受试者中，口服补充α-生育酚（400至1200 IU/d）导致血小板α-生育酚含量增加，这与PMA介导的血小板聚集的显著抑制相关（r = 0.67；P < 0.01）。补充后这些受试者的血小板对PMA刺激的PKC也表现出明显的完全抑制。
这些数据表明，口服补充达到的水平的α-生育酚掺入血小板与通过PKC依赖性机制抑制血小板聚集有关。这些观察结果可能代表了α-生育酚在预防冠状动脉疾病发展中所观察到的有益作用的一种潜在机制。
