骨髓来源细胞中的NFAT5表达会加剧动脉粥样硬化并促使巨噬细胞迁移。

NFAT5 expression in bone marrow-derived cells enhances atherosclerosis and drives macrophage migration.

作者信息

Halterman Julia A, Kwon H Moo, Leitinger Norbert, Wamhoff Brian R

机构信息

Department of Pharmacology, University of Virginia, Charlottesville VA, USA.

出版信息

Front Physiol. 2012 Aug 3;3:313. doi: 10.3389/fphys.2012.00313. eCollection 2012.

OBJECTIVE

We have previously shown that the transcription factor, nuclear factor of activated T-cells 5 (NFAT5), regulates vascular smooth muscle cell phenotypic modulation, but the role of NFAT5 in atherosclerosis is unknown. Our main objective was to determine if NFAT5 expression in bone marrow (BM)-derived cells altered atherosclerotic development and macrophage function.

METHODS AND RESULTS

NFAT5(+/-)ApoE(-/-) mice were generated for in vivo atherosclerosis studies. Following high fat diet feeding, en face analysis of the thoracic aorta established that genome-wide NFAT5 haploinsufficiency reduced atherosclerotic lesion formation by 73%. BM transplant studies revealed that transplantation of NFAT5(+/-)ApoE(-/-) marrow into NFAT5(+/+)ApoE(-/-) mice resulted in a similar 86% reduction in lesion formation. In vitro functional analysis of BM-derived macrophages demonstrated that NFAT5 is required for macrophage migration, which is a key event in the propagation of atherosclerosis.

CONCLUSION

We have identified NFAT5 in BM-derived cells as a positive regulator of atherosclerotic lesion formation and macrophage function in the vasculature.

目的

我们之前已经表明，转录因子活化T细胞核因子5（NFAT5）可调节血管平滑肌细胞表型调节，但NFAT5在动脉粥样硬化中的作用尚不清楚。我们的主要目的是确定骨髓（BM）来源细胞中NFAT5的表达是否会改变动脉粥样硬化的发展和巨噬细胞功能。

方法和结果

构建NFAT5(+/-)ApoE(-/-)小鼠用于体内动脉粥样硬化研究。高脂饮食喂养后，对胸主动脉进行整体分析表明，全基因组NFAT5单倍体不足使动脉粥样硬化病变形成减少了73%。骨髓移植研究显示，将NFAT5(+/-)ApoE(-/-)骨髓移植到NFAT5(+/+)ApoE(-/-)小鼠中，病变形成也有类似的86%的减少。对BM来源的巨噬细胞进行体外功能分析表明，NFAT5是巨噬细胞迁移所必需的，而巨噬细胞迁移是动脉粥样硬化进展中的关键事件。