Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries
Intracranial arteries of human fetuses are more resistant to hypercholesterolemia-induced fatty streak formation than extracranial arteries
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DOI：
10.1161/01.cir.99.15.2003
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发表时间：
1999-04-20
期刊：
影响因子：
37.8
通讯作者：
Palinski, W
中科院分区：
文献类型：
--
作者：
Napoli, C;Witztum, JL;Palinski, W
颅内动脉的动脉粥样硬化病变比颅外动脉的发生晚，范围小。为了研究导致这种差异的潜在机制，特别是对高胆固醇血症和LDL氧化的致动脉粥样硬化反应，我们比较了正常胆固醇血症和高胆固醇血症母亲的胎儿颅内动脉与颅外动脉中脂肪条纹形成的程度和这些非常早期病变的组成。30个油红O染色切片的辅助图像分析，每个切片来自人胎儿的大脑中动脉、基底动脉、颈总动脉和腹主动脉（自然流产和出生后12小时内死亡的早产儿;胎龄均为6.2+/-1.3个月）。免疫细胞化学法检测病变组织中巨噬细胞、载脂蛋白B和氧化低密度脂蛋白2个表位。同时测定动脉壁超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性。腹主动脉的病变数量和大小明显大于（每个切片的最大病变面积：66.5+/-10.9 x 10（3）μ m（2））和颈动脉基底动脉和大脑中动脉分别为0.4+/-0.1和0.8+/-0.2x10（3）μ m（2）; P
Background-Atherosclerotic lesions in intracranial arteries occur later and are less extensive than in extracranial arteries. To investigate potential mechanisms responsible for this difference, in particular the atherogenic response to hypercholesterolemia and LDL oxidation, we compared the extent of fatty streak formation and the composition of these very early lesions in intracranial arteries of human fetuses from normocholesterolemic and hypercholesterolemic mothers with those in extracranial arteries.Methods and Results-Lesions were quantified by computer-assisted image analysis of 30 oil red O-stained sections, each from the middle cerebral, basilar, and common carotid arteries and the abdominal aorta of human fetuses (spontaneous abortions and premature newborns who died within 12 hours of birth; both of fetal age 6.2+/-1.3 months) from 43 hypercholesterolemic mothers and 34 normocholesterolemic mothers. Macrophages, apolipoprotein B, and 2 epitopes of oxidized LDL in lesions were determined immunocytochemically. Activities of superoxide dismutase, catalase, and glutathione peroxidase in the arterial wall were also determined. Lesion numbers and sizes were dramatically greater in the abdominal aorta (area of the largest lesion per section: 66.5+/-10.9 x 10(3) mu m(2)) and the carotid (11.6+/-5.3 x 10(3) mu m(2)) than in the basilar and middle cerebral artery (0.4+/-0.1 and 0.8+/-0.2 x 10(3) mu m(2), respectively; P