T-box20 suppresses oxidized low-density lipoprotein-induced human vascular endothelial cell injury by upregulation of PPAR-γ.


BACKGROUND Atherosclerosis is a chronic inflammation disease which is initiated by endothelial cell injury Oxidized low-density lipoprotein (ox-LDL) is directly associated with chronic vascular inflammation. Many transcription factors take part in the initiation and progression of atherosclerosis. As a transcription factor mainly expressed in cardiovascular system, T-box20 (Tbx20) plays an important role in embryonic cardiovascular system development and homeostasis. However, the role of Tbx20 in endothelial cell injury and atherosclerosis is still not clear. We showed that Tbx20 might affect ox-LDL-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS First, Tbx20 expression was down regulated in the C57BL/6 mice with high-fat diet-induced artery injury, which was accompanied by elevated reactive oxygen species (ROS) generation and cell adhesion molecule expression. Second, ox-LDL led to concurrent decreased Tbx20 expression and increased levels of ROS and adhesion molecules in the HUVECs. Third, over-expression of Tbx20 by adenovirus reduced ox-LDL-induced HUVEC injury via attenuation of ROS generation and cell adhesion molecule expression. Fourth, knock down of Tbx20 by siRNA significantly increased adhesion molecule expression and decreased cell viability. Moreover, Tbx20 could directly regulate PPAR-γ expression, as shown by Tbx20 knock down and PPAR-γ inhibition, which significantly reversed Tbx20's HUVEC protection effect. CONCLUSIONS These results indicate that misregulation of Tbx20 could reduce HUVEC tolerance of ox-LDL-induced cell injury, suggesting that Tbx20 might be a crucial regulator and potential therapeutic target for atherosclerosis.

DOI: 10.1159/000354514

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@article{Shen2013Tbox20SO, title={T-box20 suppresses oxidized low-density lipoprotein-induced human vascular endothelial cell injury by upregulation of PPAR-γ.}, author={Tao Shen and Yuping Zhu and Jigar Patel and Yang Ruan and Beidong Chen and Gexin Zhao and Yuan Cao and Jing Pang and Hangbang Guo and Hongxia Li and Yong Man and Shu Wang and Jian Li}, journal={Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology}, year={2013}, volume={32 5}, pages={1137-50} }