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Chunyan Luo Decheng Wang Weifeng Huang Yinhong Song Lisha Ge Xinyue Zhang Lixue Yang Jiao Lu Xiancong Tu Qiuyun Chen Jian Yang Chengqi Xu Qing Wang 《生物化学与生物物理学报:疾病的分子基础》2021,1867(7):166130
A high level of low-density lipoprotein cholesterol (LDL) is one of the most important risk factors for coronary artery disease (CAD), the leading cause of death worldwide. However, a low concentration of LDL may be protective. Genome-wide association studies revealed that variation in ADTRP gene increased the risk of CAD. In this study, we found that a low concentration of oxidized-LDL induced the expression of ADTRP. Further analyses showed that knockdown of the expression of LDL receptor genes LDLR, CD36, or LOX-1 significantly downregulated ADTRP expression, whereas overexpression of LDLR/CD36/LOX-1 markedly increased ADTRP expression through the NF-κB pathway. Like ADTRP, LDLR, CD36 and LOX-1 were all involved in endothelial cell (EC) functions relevant to the initiation of atherosclerosis. Downregulation of LDLR/CD36/LOX-1 promoted monocyte adhesion to ECs and transendothelial migration of monocytes by increasing expression of ICAM-1, VCAM-1, E-selectin and P-selectin, decreased EC proliferation and migration, and increased EC apoptosis, thereby promoting the initiation of atherosclerosis. Opposite effects were observed with the overexpression of ADTRP and LDLR/CD36/LOX-1 in ECs. Interestingly, through the NF-κB and AKT pathways, overexpression of ADTRP significantly upregulated the expression of LDLR, CD36, and LOX-1, and knockdown of ADTRP expression significantly downregulated the expression of LDLR, CD36, and LOX-1. These data suggest that ADTRP and LDL receptors LDLR/CD36/LOX-1 positively regulate each other, and form a positive regulatory loop that regulates endothelial cell functions, thereby providing a potential protective mechanism against atherosclerosis. Our findings provide a new molecular mechanism by which deregulation of ADTRP and LDLR/CD36/LOX-1 promote the development of atherosclerosis and CAD. 相似文献
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Paek Hyo-Jin Luo Zhao-Bo Choe Hak-Myong Quan Biao-Hu Gao Kai Han Sheng-Zhong Li Zhou-Yan Kang Jin-Dan Yin Xi-Jun 《Transgenic research》2021,30(5):663-674
Transgenic Research - Herein, we investigate the high incidence of umbilical hernia and tippy-toe standing and their underlying changes in gene expression and proliferation in myostatin knockout... 相似文献
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Luo Shengxue Zhang Panli Zou Peng Wang Cong Liu Bochao Wu Cuiling Li Tingting Zhang Ling Zhang Yuming Li Chengyao 《中国病毒学》2021,36(5):1113-1123
Virologica Sinica - SARS-CoV-2 has caused more than 3.8 million deaths worldwide, and several types of COVID-19 vaccines are urgently approved for use, including adenovirus vectored vaccines.... 相似文献