P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice.
P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice.
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DOI：
10.1084/jem.191.1.189
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发表时间：
2000-01-03
期刊：
影响因子：
--
通讯作者：
Beaudet AL
中科院分区：
文献类型：
--
作者：
Collins RG;Velji R;Guevara NV;Hicks MJ;Chan L;Beaudet AL
白细胞和内皮细胞粘附分子（CAM）的表达对于炎症反应期间白细胞的迁出至关重要。炎症反应在动脉粥样硬化发展中的重要性通过在病变和病变易发区域中粘附分子、促炎细胞因子和生长因子的表达增加以及通过在炎症反应的各个方面缺陷的小鼠中的保护来指示。我们定量了细胞间粘附分子（ICAM）-1、P-选择素或E-选择素缺乏对正常饮食喂养的20周龄载脂蛋白（apo）E−/−（缺乏）小鼠动脉粥样硬化病变形成的影响。所有小鼠均为apo E−/−和CAM+/+或CAM−/−同窝小鼠，研究期间未发现不同基因型之间的体重或胆固醇水平存在差异。ICAM-1−/−小鼠的病变面积显著小于ICAM-1+/+同窝小鼠：−/−雄性为4.08 ± 0.70 mm 2，+/+雄性为5.87 ± 0.66 mm 2，−/−雌性为3.95 ± 0.65 mm 2，+/+雌性为5.59 ± 1.131 mm 2，合并P < 0.0001。在P-选择素−/−小鼠中观察到的病变面积减少幅度更大：−/−雄性为3.06 ± 1.04 mm 2，+/+雄性为5.09 ± 1.22 mm 2，−/−雌性为2.85 ± 1.26 mm 2，+/+雌性为5.60 ± 1.19 mm 2，合并P < 0.001。E-选择素缺失小鼠的病变面积减少，尽管小于ICAM-1或P-选择素所见，但仍然是显著的（−/−男性为4.54 ± 2.14 mm 2，+/+男性为5.92 ± 0.63 mm 2，−/−女性为4.38 ± 0.85 mm 2，+/+女性为5.94 ± 1.44 mm 2，合并P < 0.01）。这些结果，再加上本研究的密切控制的遗传学，表明P-选择素，ICAM-1，或E-选择素的表达减少提供了直接的保护动脉粥样硬化病变形成在这个模型中。
The expression of leukocyte and endothelial cell adhesion molecules (CAMs) is essential for the emigration of leukocytes during an inflammatory response. The importance of the inflammatory response in the development of atherosclerosis is indicated by the increased expression of adhesion molecules, proinflammatory cytokines, and growth factors in lesions and lesion-prone areas and by protection in mice deficient in various aspects of the inflammatory response. We have quantitated the effect of deficiency for intercellular adhesion molecule (ICAM)-1, P-selectin, or E-selectin on atherosclerotic lesion formation at 20 wk of age in apolipoprotein (apo) E−/− (deficient) mice fed a normal chow diet. All mice were apo E−/− and CAM+/+ or CAM−/− littermates, and no differences were found in body weight or cholesterol levels among the various genotypes during the study. ICAM-1−/− mice had significantly less lesion area than their ICAM-1+/+ littermates: 4.08 ± 0.70 mm2 for −/− males vs. 5.87 ± 0.66 mm2 for +/+ males, and 3.95 ± 0.65 mm2 for −/− females vs. 5.59 ± 1.131 mm2 for +/+ females, combined P < 0.0001. An even greater reduction in lesion area was observed in P-selectin−/− mice: 3.06 ± 1.04 mm2 for −/− males vs. 5.09 ± 1.22 mm2 for +/+ males, and 2.85 ± 1.26 mm2 for −/− females compared with 5.60 ± 1.19 mm2 for +/+ females, combined P < 0.001. The reduction in lesion area for the E-selectin null mice, although less than that seen for ICAM-1 or P-selectin, was still significant (4.54 ± 2.14 mm2 for −/− males vs. 5.92 ± 0.63 mm2 for +/+ males, and 4.38 ± 0.85 mm2 for −/− females compared with 5.94 ± 1.44 mm2 for +/+ females, combined P < 0.01). These results, coupled with the closely controlled genetics of this study, indicate that reductions in the expression of P-selectin, ICAM-1, or E-selectin provide direct protection from atherosclerotic lesion formation in this model.
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影响因子：
15.9
作者：
Dong, ZM;Chapman, SM;Wagner, DD
通讯作者：
Wagner, DD
DOI：
10.1161/01.atv.14.1.133
发表时间：
1994-01-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
NAKASHIMA, Y;PLUMP, AS;ROSS, R
通讯作者：
ROSS, R
影响因子：
8.7
作者：
Nageh, MF;Sandberg, ET;Beaudet, AL
通讯作者：
Beaudet, AL
影响因子：
64.8
作者：
Mach, F;Schönbeck, U;Libby, P
通讯作者：
Libby, P
影响因子：
82.9
作者：
Guevara, NV;Kim, HS;Chan, L
通讯作者：
Chan, L