OXIDATIVELY MODIFIED LOW-DENSITY LIPOPROTEINS - A POTENTIAL ROLE IN RECRUITMENT AND RETENTION OF MONOCYTE MACROPHAGES DURING ATHEROGENESIS
OXIDATIVELY MODIFIED LOW-DENSITY LIPOPROTEINS - A POTENTIAL ROLE IN RECRUITMENT AND RETENTION OF MONOCYTE MACROPHAGES DURING ATHEROGENESIS
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DOI：
10.1073/pnas.84.9.2995
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发表时间：
1987-05-01
影响因子：
11.1
通讯作者：
STEINBERG, D
中科院分区：
文献类型：
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作者：
QUINN, MT;PARTHASARATHY, S;STEINBERG, D
该实验室以前的研究证实，低密度脂蛋白(LDL)与培养的内皮细胞、平滑肌细胞或巨噬细胞孵育后，经历了自由基催化的氧化修饰，从而产生脂质过氧化和低密度脂蛋白(LDL)分子结构的广泛变化。氧化修饰的低密度脂蛋白强烈抑制小鼠常驻腹膜巨噬细胞的趋化反应。目前的研究表明，His氧化的低密度脂蛋白不抑制小鼠单核细胞的运动，实际上对人单核细胞具有趋化活性；氧化的低密度脂蛋白的趋化活性存在于脂质部分。这些发现使我们能够提出一种致病顺序，即血浆低密度脂蛋白水平升高，随后动脉壁氧化修饰，可以充分解释载脂泡沫细胞的产生和脂肪牛排的启动，脂肪牛排是动脉粥样硬化形成中最早明确的病变。
Previous studies in this laboratory established that low density lipoprotein (LDL) incubated with cultured endothelial cells, smooth muscle cells, or macrophages undergoes a free radical-catalyzed oxidative modification that generates lipid peroxides and extensive structural changes in the LDL molecule. The oxidatively modified LDL strongly inhibited chemotactic responses of the mouse resident peritoneal macrophage. The present studies show that his oxidized LDL does not inhibit the motility of mouse monocytes and actually exhibits a chemotactic activity for human monocytes; the chemotactic activity of the oxidized LDL resides in the lipid fraction. These findings allow us to propose a pathogenetic sequence by which elevated plasma LDL levels, followed by oxidative modification in the arterial wall, could sufficiently account for the generation of the lipid-laden foam cells and the initiation of the fatty steak, the earliest well-defined lesion in atherogenesis.