Lipid retention in the arterial wall of two mouse strains with different atherosclerosis susceptibility
Lipid retention in the arterial wall of two mouse strains with different atherosclerosis susceptibility
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DOI：
10.1194/jlr.m400092-jlr200
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发表时间：
2004-06-01
影响因子：
6.5
通讯作者：
Shi, WB
中科院分区：
文献类型：
--
作者：
Brown, MD;Jin, L;Shi, WB
LDL在动脉壁内皮下层的沉积是动脉粥样硬化发展的初始事件。沉积的LDL经过动脉壁细胞的氧化修饰成为氧化LDL，从而促进动脉粥样硬化的形成。利用对动脉粥样硬化易感性有明显差异的小鼠品系C57BL/6J （B6）和C3H/HeJ (C3H)，我们确定了载脂蛋白B (apoB)-脂蛋白内皮下保留的变化是否构成动脉粥样硬化的遗传成分。在泡沫细胞形成之前，用Western blot方法定量检测主动脉壁中载脂蛋白ob的存在。在饮食和载脂蛋白e缺乏模型中，与C3H小鼠相比，B6小鼠的主动脉壁载脂蛋白ob增加了2倍。这种增加不能归因于两种菌株血浆脂质水平的差异。在体外，与B6小鼠内皮细胞相比，C3H小鼠内皮细胞吸收更多的乙酰化和氧化LDL，而不是天然LDL，并将更多的天然LDL转化为氧化LDL。C3H小鼠主动脉壁清道夫受体A的表达高于B6小鼠。因此，含载脂蛋白的内皮下保留的差异不能解释B6和C3H小鼠动脉粥样硬化易感性的显著差异，内皮细胞可能在减轻动脉壁脂质积累方面发挥作用。
LDL deposition in the subendothelium of arterial walls is the initial event in the development of atherosclerosis. The deposited LDL undergoes oxidative modification by arterial wall cells to become oxidized LDL and consequently contributes to atherosclerotic formation. Using mouse strains C57BL/6J (B6) and C3H/HeJ (C3H), which differ markedly in susceptibility to atherosclerosis, we determined whether variation in subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins constitutes a genetic component in atherosclerosis. Lipoprotein retention was quantitated by Western blot analysis to detect the presence of apoB in aortic walls before foam cells developed. In both dietary and apoE-deficient models, B6 mice exhibited up to a 2-fold increase of apoB in the aortic wall compared with C3H mice. This increase could not be attributed to differences in plasma lipid levels of the two strains. In vitro, endothelial cells from C3H mice took up more acetylated and oxidized LDL but not native LDL and converted more native LDL to oxidized LDL than did endothelial cells from B6 mice. C3H mice expressed more scavenger receptor A in their aortic wall than B6 mice. Thus, variation in the subendothelial retention of apoB-containing lipoproteins cannot explain the dramatic difference in atherosclerosis susceptibility between B6 and C3H mice, and endothelial cells may play a role in alleviating lipid accumulation in arterial walls.