Egr-1 deficiency in bone marrow-derived cells reduces atherosclerotic lesion formation in a hyperlipidaemic mouse model
Egr-1 deficiency in bone marrow-derived cells reduces atherosclerotic lesion formation in a hyperlipidaemic mouse model
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DOI：
10.1093/cvr/cvq032
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发表时间：
2010-05-01
影响因子：
10.8
通讯作者：
Bea, Florian
中科院分区：
文献类型：
--
作者：
Albrecht, Claudia;Preusch, Michael R.;Bea, Florian
早期生长反应基因-1（Egr-1）调节心血管疾病重要基因的表达。在动脉粥样硬化病变中，Egr-1在平滑肌细胞、内皮细胞和巨噬细胞中表达。由于巨噬细胞在动脉粥样硬化病变的发生和发展中起着关键作用，本研究探讨了Egr-1缺陷的骨髓来源的细胞在动脉粥样硬化的发展中的作用，从Egr-1缺陷小鼠和野生型对照小鼠的骨髓移植到致死辐射LDL受体无效小鼠。在高脂饮食26周后，评估了受体主动脉窦内动脉粥样硬化病变的大小。与对照组相比，接受Egr-1缺陷骨髓的小鼠的病变尺寸显著减小。这些小鼠的病变中含有较少的巨噬细胞，并减少了血管细胞粘附分子-1（VCAM-1）、组织因子以及转化生长因子受体II型（Egr-1的靶基因）的表达。Egr-1缺陷的腹腔巨噬细胞，脂多糖刺激后，与野生型controls.This研究表明，骨髓来源的Egr-1促进巨噬细胞的积累，动脉粥样硬化病变的发展，和病变的复杂性相比，VCAM-1和组织因子mRNA的表达下降，在体外分析，这些结果得到了验证。
Early growth response gene-1 (Egr-1) regulates the expression of genes important to cardiovascular disease. Within atherosclerotic lesions, Egr-1 is expressed in smooth muscle cells, endothelial cells, and macrophages. Since macrophages play a pivotal role in atherosclerotic lesion initiation and progression, this study investigated the effects of Egr-1 deficiency within bone marrow-derived cells on the development of atherosclerosis in a hyperlipidaemic mouse model.Bone marrow from Egr-1-deficient mice and wild-type controls was transplanted into lethally irradiated LDL receptor null mice. After 26 weeks on a high fat diet, atherosclerotic lesion size within the aortic sinus of recipients was evaluated. Mice receiving Egr-1-deficient bone marrow had significantly decreased lesion size compared with controls. Lesions of these mice contained fewer macrophages and had reduced expression of vascular cell adhesion molecule-1 (VCAM-1), tissue factor, as well as transforming growth factor receptor type II, which are target genes of Egr-1. These results were validated by in vitro analysis of Egr-1-deficient peritoneal macrophages which, after lipopolysaccharide stimulation, had decreased VCAM-1 and tissue factor mRNA expression compared with wild-type controls.This study demonstrates that bone marrow-derived Egr-1 promotes macrophage accumulation, atherosclerotic lesion development, and lesion complexity.