Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice
Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice
复制标题
DOI：
10.1016/j.vph.2010.09.004
复制
发表时间：
2010-11-01
影响因子：
4
通讯作者：
Lee, Kwan-Woo
中科院分区：
文献类型：
--
作者：
Choi, Sung-E;Jang, Hyun-Ju;Lee, Kwan-Woo
内皮细胞功能障碍可能在包括动脉粥样硬化在内的各种血管疾病的发展中起重要作用。在这里，我们研究了氯化锂（Lid），一种糖原合成酶激酶-3 β（GSK-3 β）的抑制剂，是否可以对抗ApoE（-/-）小鼠高脂饮食诱导的动脉粥样硬化。将10周龄的雄性小鼠随机分为四组：正常食物饮食、高脂肪饮食（即，20%脂肪和0.5%胆固醇），高脂饮食与LiCl处理6周和高脂饮食与LiCl处理14周。血浆曲线的检查表明，血糖水平显着降低氯化锂治疗。补充氯化锂可显著降低主动脉和主动脉根部的动脉粥样硬化病变形成。氯化锂治疗还降低了血管细胞粘附分子（VCAM）-1的表达和巨噬细胞浸润到主动脉瓣内的动脉粥样硬化病变区域。此外，通过TDZD-8、SB 216763和LiCl抑制GSK-3 β，以及用无催化活性的GSK-3 β进行腺病毒转导，通过抑制JNK活性和人脐静脉内皮细胞（HUVEC）中I κ-B α的降解来降低棕榈酸酯诱导的VCAM-1表达。本研究的结果表明，氯化锂抑制棕榈酸诱导的细胞粘附分子在HUVECs的表达，并减少ApoE（-/-）小鼠高脂饮食诱导的动脉粥样硬化。因此，GSK-3 β可能参与Apoe（-/-）小鼠高脂饮食诱导的动脉粥样硬化的发展。(C)2010年爱思唯尔公司All rights reserved.
Endothelial cell dysfunction may play an important role in the development of various vascular diseases, including atherosclerosis. Here we investigated whether lithium chloride (Lid), an inhibitor of glycogen synthase kinase-3 beta (GSK-3 beta), could counteract atherosclerosis induced by a high-fat diet in ApoE(-/-) mice. Ten-week-old male mice were randomly divided into four groups: normal chow diet, high-fat diet (i.e., 20% fat and 0.5% cholesterol), high-fat diet with LiCl treatment for 6 weeks and high-fat diet with LiCl treatment for 14 weeks. Examination of plasma profiles indicated that blood glucose levels were significantly decreased by LiCl treatment. Supplementation with LiCl dramatically reduced atherosclerotic lesion formation in the aorta and aortic root. LiCl treatment also decreased vascular cell adhesion molecule (VCAM)-1 expression and macrophage infiltration into atherosclerotic lesion areas within the aortic valve. In addition, inhibition of GSK-3 beta by TDZD-8, SB216763, and LiCl, as well as adenoviral transduction with a catalytically inactive GSK-3 beta, reduced palmitate-induced VCAM-1 expression through inhibition of JNK activity and degradation of I kappa-B alpha in human umbilical vein endothelial cells (HUVECs). The results of the present study suggest that LiCl alleviates palmitate-induced cell adhesion molecule expression in HUVECs and decreases atherosclerosis induced by a high-fat diet in ApoE(-/-) mice. Thus, GSK-3 beta may be involved in the development of atherosclerosis induced by a high-fat diet in ApoE(-/-) mice. (C) 2010 Elsevier Inc. All rights reserved.