in situ immunocytochemical study of adhesion molecules expressed on endothelium in atherosclerosis-prone mouse

易发生动脉粥样硬化的小鼠内皮上表达的粘附分子的原位免疫细胞化学研究

• 批准号: 07457051
• 负责人: NAKASHIMA Yutaka
• 金额: $ 4.61万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457051/
• 关键词: atherosclerosis; ApoE-deficient mouse; VCAM-1; ICAM-1; PECAM-1; in situ immnocytochemistry; monocyte; shear stress; apollipoproteinE欠損マウス; E-selectin; P-selectin; in situ免疫染色; 接着因子; 遺伝子欠損マウス; in situ免疫法

Focal recruitment of monocytes and lymphocytes is one of the earliest detectable cellular responses in the formation of lesions of atherosclerosis. This localized accumulation of leukocytes is a multistep process in which the endothelium remains intact and may regulate leukocyte recruitment by expressing specific adhesion molecules. To examine the relationship of adhesion molecule expression to initiation factors and the sites of lesion formation, we have analyzed the expression of VCAM-1, ICAM-1, and PECAM-1 en face on the aortic endothelium of control mice and homozygous apolipoprotein E-deficient mice that develop complex lesions of atherosclerosis similar to those in humans. In control mice, VCAM-1 staining is weak and limited to sites of altered blood flow. In contrast, in the ApoE-deficient mice, VCAM-1 appears to be localized over the surface of groups of endothelial cells in lesion-prone sites. Its expression precedes lesion formation, and increased expression above control levels appears to correlate with extent of exposure to plasma cholesterol. Although ICAM-1 is the most prominent adhesion molecule in lesion-prone sites, its expression appears to be independent of plasma cholesterol levels and is upregulated in both ApoE -/- and control mice. At lesion-prone sites asociated with altered blood flow, ICAM-1 is located over the surface of each endothelial cell and on microvilli, whereas it is confined to the cell periphery in nonlesion-prone sites. PECAM-1 is localized at the cell periphery throughout the aorta, and its expression does not appear to be regulated. Thus, the levels, localization, and characteristics of expression of VCAM-1, ICAM-1, and PECAM-1 appear to be differentially regulated. Upregulation of VCAM-1 and ICAM-1 is associated with sites of lesion formation.

单核细胞和淋巴细胞的局灶性募集是动脉粥样硬化病变形成中最早可检测到的细胞反应之一。这种白细胞的局部积聚是一个多步骤的过程，其中内皮保持完整，并可通过表达特异性粘附分子来调节白细胞募集。为了研究粘附分子表达与起始因子和病变形成部位的关系，我们分析了对照小鼠和纯合子载脂蛋白E缺陷小鼠主动脉内皮上VCAM-1、ICAM-1和PECAM-1的表达，这些小鼠发生了与人类相似的复杂动脉粥样硬化病变。在对照小鼠中，VCAM-1染色较弱，仅限于血流改变的部位。相比之下，在Apoe缺陷小鼠中，VCAM-1似乎定位于易损伤部位的内皮细胞群表面。它的表达先于病变形成，并且高于对照水平的表达增加似乎与血浆胆固醇的暴露程度相关。虽然ICAM-1是最突出的粘附分子在病变倾向的网站，它的表达似乎是独立的血浆胆固醇水平，并上调ApoE -/-和对照小鼠。在与血流改变相关的病变倾向部位，ICAM-1位于每个内皮细胞的表面和微绒毛上，而在非病变倾向部位，ICAM-1仅限于细胞周边。PECAM-1位于整个主动脉的细胞外周，其表达似乎不受调节。因此，VCAM-1、ICAM-1和PECAM-1的表达水平、定位和特征似乎受到差异调节。VCAM-1和ICAM-1的上调与病变形成部位相关。