对氧化脂蛋白的内皮反应决定了小鼠对动脉样硬化的遗传易感性
W Shi1, M E Haberland, M L Jien
1Department of Medicine, University of California Los Angeles 90095- 1679, USA.
Circulation
|July 6, 2000
概括
血管细胞对最小修饰的LDL (MM-LDL) 的反应方式的遗传差异有助于动脉样硬化易感性. 这项研究强调了血管壁作为对这种疾病的遗传影响的关键位置.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 氧化低密度脂蛋白 (LDL) 在子内皮层积聚,促进炎症并导致动脉样硬化.
- 对最小修饰的LDL (MM-LDL) 的内皮细胞 (EC) 反应的变化可能代表动脉样硬化的遗传组成部分.
研究的目的:
- 调查内皮细胞对MM-LDL反应的遗传变异是否影响动脉样硬化易感性.
- 确定不同小鼠菌株的EC中受MM-LDL影响的特定炎症和氧化应激基因.
主要方法:
- 利用一种新的探索技术,从具有不同易受饮食诱导动脉样硬化症的杂交小鼠菌株中分离出大动脉内皮细胞 (ECs).
- 通过测量关键基因的表达来评估EC对MM-LDL的反应:单细胞化疗蛋白-1 (MCP-1),巨细胞殖民地刺激因子 (M-CSF) 和血氧酶-1 (HO-1).
- 将EC对MM-LDL的反应与对脂聚糖 (LPS) 的反应进行比较,以区分特定的MM-LDL影响.
主要成果:
- 来自对动脉样硬化敏感的小鼠菌株 (C57BL/6J) 的内皮细胞在MM-LDL暴露时显著诱导了MCP-1,M-CSF和HO-1.
- 来自抗动脉样硬化的小鼠菌株 (C3H/HeJ) 的内皮细胞在对MM-LDL的反应中显示出这些基因的诱导最小或不存在.
- 两种小鼠菌株的ECs对脂多糖体表现出类似的反应,表明MM-LDL反应性的特定差异.
结论:
- 影响动脉样硬化的遗传因素在血管壁的水平上起作用.
- 不同的内皮细胞对MM-LDL的反应是动脉样硬化易感性的重要遗传决定因素.
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