Li Wei, Xu Li-Hua, Forssell Claes, Sullivan Jerome L, Yuan Xi-Ming
Division of Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Exp Biol Med (Maywood). 2008 Jul;233(7):818-26. doi: 10.3181/0711-RM-320. Epub 2008 Apr 29.
Accumulation of tissue iron has been implicated in development of atherosclerotic lesions mainly because of increased iron-catalyzed oxidative injury. However, it remains unknown whether cellular iron import and storage in human atheroma are related to human atheroma development. We found that transferrin receptor 1 (TfR1), a major iron importer, is highly expressed in foamy macrophages and some smooth muscle cells in intimal lesions of human carotid atheroma, mainly in cytoplasmic accumulation patterns. In 52 human carotid atherosclerotic lesions, TfR1 expression was positively correlated with macrophage infiltration, ectopic lysosomal cathepsin L, and ferritin expression. Highly expressed TfR1 and ferritin in CD68-positive macrophages were significantly associated with development and severity of human carotid plaques, smoking, and patient's symptoms. The findings suggest that pathologic macrophage iron metabolism may contribute to vulnerability of human atheroma, established risk factors, and their clinical symptoms. The cytoplasmic overexpression of TfR1 may be the result of lysosomal dysfunction and ectopic accumulation of lysosomal cathepsin L caused by atheroma-relevant lipids in atherogenesis.
组织铁的蓄积与动脉粥样硬化病变的发展有关，主要是因为铁催化的氧化损伤增加。然而，人类动脉粥样硬化中细胞铁的摄取和储存是否与人类动脉粥样硬化的发展相关仍不清楚。我们发现，主要的铁摄取蛋白转铁蛋白受体1（TfR1）在人类颈动脉粥样硬化内膜病变的泡沫巨噬细胞和一些平滑肌细胞中高表达，主要呈细胞质积聚模式。在52例人类颈动脉粥样硬化病变中，TfR1表达与巨噬细胞浸润、异位溶酶体组织蛋白酶L和铁蛋白表达呈正相关。CD68阳性巨噬细胞中高表达的TfR1和铁蛋白与人类颈动脉斑块的发展和严重程度、吸烟及患者症状显著相关。这些发现表明，病理性巨噬细胞铁代谢可能导致人类动脉粥样硬化的易损性、既定危险因素及其临床症状。TfR1的细胞质过表达可能是动脉粥样硬化形成过程中与动脉粥样硬化相关的脂质导致溶酶体功能障碍和溶酶体组织蛋白酶L异位积聚的结果。
