Bobryshev Y V, Lord R S, Watanabe T, Ikezawa T
Surgical Professorial Unit, St. Vincent's Hospital, Darlinghurst NSW, Australia.
Cardiovasc Res. 1998 Oct;40(1):191-205. doi: 10.1016/s0008-6363(98)00141-2.
Various cell adhesion molecules are expressed in atherogenesis and the significance of their involvement in atherosclerotic lesion formation is well appreciated. In the present work, we examined whether the Ca(2+)-dependent cell adhesion molecule E-cadherin is also involved in atherogenesis.
Specimens of carotid artery and aorta were obtained at operation. Expression of E-cadherin was studied by an immunohistochemical method. The nature of E-cadherin-expressing cells was examined by comparative analysis of consecutive sections and by a double immunostaining procedure. An immunohistochemical approach was also applied to examine how the accumulation of oxidised low density lipoproteins (LDL) by intimal cells is associated with E-cadherin expression.
No E-cadherin+ cells were found in normal non-atherosclerotic intima but E-cadherin+ cells were present in 96% of the atherosclerotic lesions. In atherosclerotic intima, E-cadherin was expressed by intimal cells showing varying degrees of transformation into foam cells. These E-cadherin+ cells also contained oxidised LDL in their cytoplasm. Differing numbers of CD68+ foam cells (15% to 60%) expressed E-cadherin but all the CD68+ macrophages without signs of transformation into foam cells were negative for E-cadherin. Neither smooth muscle cells nor foam cells of smooth muscle cell origin (smooth muscle alpha-actin+) were found to be positive for E-cadherin. T-cells (CD3+) and endothelial cells (von Willebrand factor+) were also negative for E-cadherin. Only a few vascular dendritic cells (S-100+) expressed E-cadherin and their expression was weak. We also found that a large proportion (40% to 85%) of E-cadherin+ cells did not stain with any cell-type specific markers.
The finding that E-cadherin is expressed in atherosclerotic lesions expands our knowledge of cell adhesion molecules involved in atherogenesis. That E-cadherin is expressed in intimal cells transforming into foam cells suggests that lipid accumulation might be associated with the alteration and reorganisation of cell-to-cell interactions in atherogenesis. The present observations might assist in understanding the mechanisms associated with intracellular lipid accumulation.
多种细胞黏附分子在动脉粥样硬化形成过程中表达，其参与动脉粥样硬化病变形成的意义已得到充分认识。在本研究中，我们检测了钙离子依赖性细胞黏附分子E-钙黏蛋白是否也参与动脉粥样硬化形成。
手术中获取颈动脉和主动脉标本。采用免疫组织化学方法研究E-钙黏蛋白的表达。通过连续切片的对比分析和双重免疫染色程序检测表达E-钙黏蛋白的细胞的性质。还应用免疫组织化学方法检测内膜细胞对氧化型低密度脂蛋白（LDL）的摄取与E-钙黏蛋白表达之间的关系。
在正常非动脉粥样硬化内膜中未发现E-钙黏蛋白阳性细胞，但在96%的动脉粥样硬化病变中存在E-钙黏蛋白阳性细胞。在动脉粥样硬化内膜中，E-钙黏蛋白由内膜细胞表达，这些细胞显示出不同程度地转化为泡沫细胞。这些E-钙黏蛋白阳性细胞的细胞质中也含有氧化型LDL。不同数量的CD68阳性泡沫细胞（15%至60%）表达E-钙黏蛋白，但所有未显示转化为泡沫细胞迹象的CD68阳性巨噬细胞E-钙黏蛋白呈阴性。未发现平滑肌细胞或平滑肌细胞来源的泡沫细胞（平滑肌α-肌动蛋白阳性）E-钙黏蛋白呈阳性。T细胞（CD3阳性）和内皮细胞（血管性血友病因子阳性）E-钙黏蛋白也呈阴性。只有少数血管树突状细胞（S-100阳性）表达E-钙黏蛋白，且其表达较弱。我们还发现，很大比例（40%至85%）的E-钙黏蛋白阳性细胞不被任何细胞类型特异性标志物染色。
E-钙黏蛋白在动脉粥样硬化病变中表达这一发现扩展了我们对参与动脉粥样硬化形成的细胞黏附分子的认识。E-钙黏蛋白在内膜细胞转化为泡沫细胞中表达，提示脂质蓄积可能与动脉粥样硬化形成过程中细胞间相互作用的改变和重组有关。目前的观察结果可能有助于理解与细胞内脂质蓄积相关的机制。
