Adhesion molecules and atherogenesis
Adhesion molecules and atherogenesis
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DOI：
10.1046/j.1365-201x.2001.00882.x
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发表时间：
2001-09-01
期刊：
影响因子：
--
通讯作者：
Ley, K
中科院分区：
文献类型：
--
作者：
Huo, Y;Ley, K
动脉粥样硬化是一种血管壁的炎性疾病，其特征是单核细胞浸润，以响应促动脉粥样硬化因子，如氧化脂质。最近，已经探索了特定粘附分子在这一过程中的作用。覆盖动脉粥样硬化病变的内皮表达P-选择素，肩部区域表达血管细胞粘附分子-1（VCAM-1）和细胞间粘附分子-1（ICAM-1），其也在不易于斑块发展的区域的内皮上表达。心绞痛或外周动脉粥样硬化性疾病患者血清可溶性P-选择素、ICAM-1和VCAM-1水平升高。在体外系统中使用单核细胞在剪切流下对精氨酸激活的内皮细胞进行重建，表明P-选择素、L-选择素、VCAM-1及其配体、VLA-4整联蛋白和CD 18整联蛋白参与。对动脉粥样硬化（apoE-/-）小鼠的离体灌注颈动脉中单核细胞粘附的研究显示，P-选择素及其配体P-选择素糖蛋白-1（PSGL-1）主要参与滚动，VLA-4和VCAM-1主要参与牢固粘附。与这些发现一致，也缺乏P-选择素的apoE-/-小鼠显示出显著减小的动脉粥样硬化病变尺寸，并且几乎完全保护血管损伤后的新生内膜生长。在低密度脂蛋白（LDL）受体缺陷（LDLR-/-）小鼠中也观察到较轻的影响。在高胆固醇/胆酸盐模型中，还显示了ICAM-1和CD 18整联蛋白的作用，但这有待于在更多的生理模型中证实。在apoE-/-或LDLR-/-小鼠中通过抗体或肽短暂阻断VLA-4/VCAM-1粘附途径可减少病变中单核细胞和脂质蓄积。这些数据表明，P-选择素，PSGL-1，VLA-4和VCAM-1是参与单核细胞募集到动脉粥样硬化病变的最重要的粘附分子。
Atherosclerosis is an inflammatory disease of the vessel wall characterized by monocyte infiltration in response to pro-atherogenic factors such as oxidized lipids. Recently, the role of specific adhesion molecules in this process has been explored. The endothelium overlying atherosclerotic lesions expresses P-selectin and the shoulder regions express vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), which is also expressed on endothelium in regions not prone to plaque development. Serum levels of soluble P-selectin, ICAM-1 and VCAM-1 are elevated in patients with angina pectoris or peripheral atherosclerotic disease. Reconstituted in vitro systems using monocytes on cytokine-activated endothelial cells under shear flow suggested the involvement of P-selectin, L-selectin, VCAM-1, its ligand, VLA-4 integrin and CD18 integrins. Studies of monocyte adhesion in isolated perfused carotid arteries harvested from atherosclerotic (apoE-/-) mice show a predominant involvement of P-selectin and its ligand P-selectin glycoprotein-1 (PSGL-1) in rolling and of VLA-4 and VCAM-1 in firm adhesion. Consistent with these findings, apoE-/- mice that are also deficient for P-selectin show significantly reduced atherosclerotic lesion sizes and are almost completely protected from neointimal growth after vascular injury. Milder effects are also seen in the low-density lipoprotein (LDL) receptor deficient (LDLR-/-) mouse. In a high cholesterol/ cholate model, a role of ICAM-1 and CD18 integrins was also shown, but this awaits confirmation in more physiologic models. Transient blockade of the VLA-4/VCAM-1 adhesion pathway by antibodies or peptides in apoE-/- or LDLR-/- mice reduced monocyte and lipid accumulation in lesions. These data suggest that P-selectin, PSGL-1, VLA-4 and VCAM-1 are the most important adhesion molecules involved in monocyte recruitment to atherosclerotic lesions.