Macrophages, lipid oxidation, ceroid accumulation and alpha-tocopherol depletion in human atherosclerotic lesions.
Macrophages, lipid oxidation, ceroid accumulation and alpha-tocopherol depletion in human atherosclerotic lesions.
复制标题
人类动脉粥样硬化病变中的巨噬细胞、脂质氧化、蜡样积累和α-生育酚消耗。
作者：
K. H. Carpenter;C. J. V. D. Veen;S. Taylor;S. J. Hardwick;K. Clare;Laszlo Hegyi;Malcolm J. Mitchinson
分析了不同组织学阶段动脉粥样硬化病变的尸检样本。蜡样物质存在于所有病变中，在充满脂质的巨噬细胞泡沫细胞内和晚期病变的动脉粥样硬化核心的细胞外。病变内膜中7 β-羟基胆固醇、26-羟基胆固醇和羟基十八碳二烯酸的平均水平均显著高于正常内膜。在正常内膜中，羟胆固醇水平非常低或检测不到。脂肪条纹显示7 β-羟基胆固醇与胆固醇的比例最高，亚油酸与油酸的比例最低，表明这种类型的病变经历了最大的自由基活性。26-羟基胆固醇水平，细胞色素P-450酶甾醇26-羟化酶的产物，和26-羟基胆固醇胆固醇的比例在晚期病变中显着高于中期病变或脂肪条纹。α-生育酚与胆固醇水平的比率在正常内膜中变化很大，但在病变中始终较低，特别是那些富含巨噬细胞泡沫细胞的病变，这表明病变中的氧化活性可能仅在α-生育酚耗尽后导致病变成分的显著氧化。巨噬细胞死亡是晚期病变的特征，存在凋亡小体，偶尔在病变中观察到完整的凋亡细胞。巨噬细胞、脂质氧化、α-生育酚耗竭、蜡样物质积累和晚期病变中巨噬细胞死亡之间的这些显著相关性强烈支持氧化损伤在动脉粥样硬化中的作用，并使α-生育酚膳食补充剂可能减缓人类动脉粥样硬化进展的想法变得可信。
Necropsy samples of atherosclerotic lesions of different histological stages have been analysed. Ceroid was present in all the lesions, within lipid-laden macrophage foam cells and extracellularly in the atheromatous core of advanced lesions. Mean levels of 7 beta-hydroxycholesterol, 26-hydroxycholesterol and hydroxyoctadecadienoic acids were all significantly greater in lesions than in normal intima. Levels of hydroxycholesterols were very low or undetectable in normal intima. Fatty streaks showed the highest ratio of 7 beta-hydroxycholesterol to cholesterol, and the lowest ratio of linoleate to oleate, suggesting that this type of lesion experiences the greatest free radical activity. Levels of 26-hydroxycholesterol, a product of the cytochrome P-450 enzyme sterol 26-hydroxylase, and the ratio of 26-hydroxycholesterol to cholesterol were significantly higher in advanced lesions than in intermediate lesions or fatty streaks. The ratio of alpha-tocopherol to cholesterol levels varied widely in normal intima but was consistently low in lesions, especially those rich in macrophage foam cells, suggesting that oxidative activity in the lesion may lead to significant oxidation of the lesion constituents only after alpha-tocopherol has been depleted. Macrophage death was a characteristic feature of advanced lesions, with apoptotic bodies present, and occasionally, intact apoptotic cells were seen in lesions. These striking correlations between macrophages, lipid oxidation, alpha-tocopherol depletion, ceroid accumulation, and macrophage death in advanced lesions, strongly support a role for oxidative damage in atherosclerosis, and lend credence to the idea that alpha-tocopherol dietary supplementation may slow the progression of atherosclerosis in humans.