Kitagawa Kazuo, Matsumoto Masayasu, Sasaki Tsutomu, Hashimoto Hiroyuki, Kuwabara Keisuke, Ohtsuki Toshiho, Hori Masatsugu
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, Yamadaoka, Suita-city, Osaka 565-0871, Japan.
Atherosclerosis. 2002 Feb;160(2):305-10. doi: 10.1016/s0021-9150(01)00587-1.
Recent clinical evidence has indicated that the level of soluble ICAM-1 (sICAM-1) is correlated with the severity of atherosclerosis and can predict future cardiovascular events. Here, using apolipoprotein E (APOE)-deficient mice, we investigated the level of sICAM-1 in parallel with endothelial ICAM-1 expression and aortic atherosclerosis. We also examined the effect of ICAM-1 deficiency during the progression of atherosclerosis using double knockout mice. The level of sICAM-1 increased significantly in parallel with the progression of atherosclerosis in APOE-deficient mice, while the sICAM-1 level remained constant in wild-type mice from 3 to 10 months of age. ICAM-1 staining was detected in virtually all endothelial cells, however, ICAM-1 was expressed strongly in the endothelium overlying atheromatous palque in APOE-deficient mice. Deficiency of ICAM-1 in APOE-deficient mice significantly reduced lesions after 5 and 10 months. The present study supported the notion that the level of sICAM-1 is closely related with the severity of atherosclerosis and cardiovascular events, and also suggested that inhibition of ICAM-1 can delay the progression of atherosclerosis.
近期临床证据表明，可溶性细胞间黏附分子-1（sICAM-1）水平与动脉粥样硬化的严重程度相关，且能够预测未来心血管事件。在此，我们利用载脂蛋白E（APOE）缺陷小鼠，研究了sICAM-1水平与内皮细胞ICAM-1表达及主动脉粥样硬化的关系。我们还利用双敲除小鼠研究了ICAM-1缺陷在动脉粥样硬化进展过程中的作用。在APOE缺陷小鼠中，sICAM-1水平随动脉粥样硬化进展显著升高，而在3至10月龄的野生型小鼠中，sICAM-1水平保持恒定。几乎在所有内皮细胞中均检测到ICAM-1染色，但在APOE缺陷小鼠的动脉粥样斑块上方的内皮细胞中，ICAM-1表达强烈。APOE缺陷小鼠中ICAM-1的缺失在5个月和10个月后显著减少了病变。本研究支持sICAM-1水平与动脉粥样硬化严重程度及心血管事件密切相关的观点，同时也表明抑制ICAM-1可延缓动脉粥样硬化的进展。
