Combined role of P- and E-selectins in atherosclerosis
Combined role of P- and E-selectins in atherosclerosis
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DOI：
10.1172/jci3001
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发表时间：
1998-07-01
影响因子：
15.9
通讯作者：
Wagner, DD
中科院分区：
文献类型：
--
作者：
Dong, ZM;Chapman, SM;Wagner, DD
P-和E-选择素是介导白细胞外渗的第一步的粘附分子。因为它们在白细胞粘附中的功能是重叠的，我们假设这些选择素可能对动脉粥样硬化病变的发展有联合作用。我们在低密度脂蛋白受体（LDLR）缺陷的背景下培育了P-和E-选择素双缺陷小鼠，（LDLR-/- P/E-/-），并将这些小鼠的病变发展与两种选择素的野生型小鼠进行比较（LDLR-/- P/E+/+），服用致动脉粥样硬化饮食8周后，LDLR-/- P/E-/-小鼠在主动脉窦中产生脂肪条纹，其比LDLR-/- P/E+/+小鼠的小五倍。LDLR-/- P/E+/+和LDLR-/- P/E-/-小鼠之间脂肪条纹中的巨噬细胞密度相当。饮食22周后，病变扩散到整个主动脉，但这一过程在LDLR-/- P/E-/-小鼠中延迟。在37周的饮食，病变进展到纤维斑块阶段，在两种基因型，但是，在LDLR-/- P/E-/-小鼠的主动脉窦病变小40%，比LDLR-/- P/E +/+小鼠钙化少。我们的研究结果表明，P-和E-选择素一起发挥重要作用，在早期和晚期阶段的动脉粥样硬化病变的发展。
P- and E-selectins are adhesion molecules mediating the first step in leukocyte extravasation. Because their function in leukocyte adhesion is overlapping, we hypothesized that there might be a combined effect of these selectins on the development of atherosclerotic lesions. We bred P- and E-selectin-double-deficient mice onto the low-density lipoprotein receptor (LDLR)-deficient background (LDLR-/- P/E-/-) and compared lesion development in these mice to that in mice wild type for both selectins (LDLR-/- P/E+/+), After 8 wk on atherogenic diet, the LDLR-/- P/E-/- mice developed fatty streaks in the aortic sinus that were five times smaller than those in LDLR-/- P/E+/+ mice. The density of macrophages in the fatty streaks was comparable between LDLR-/- P/E+/+ and LDLR-/- P/E-/- mice. After 22 wk on the diet, the lesions spread throughout the aorta but this process was delayed in LDLR-/- P/E-/- mice. At 37 wk on diet, the lesions progressed to the fibrous plaque stage in both genotypes, However, the lesions in the aortic sinus in LDLR-/- P/E-/- mice were 40% smaller and less calcified than those of LDLR-/- P/E +/+ mice. Our results suggest that P- and E-selectins together play an important role in both early and advanced stages of atherosclerotic lesion development.