Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway

被引:35
作者
Guo, Wei [1 ,6 ,7 ]
Zhang, Huiping [2 ]
Yang, Anning [1 ,6 ,7 ]
Ma, Pengjun [1 ,6 ,7 ]
Sun, Lei [1 ,6 ,7 ]
Deng, Mei [1 ,6 ,7 ]
Mao, Caiyan [1 ,6 ,7 ]
Xiong, Jiantuan [4 ]
Sun, Jianmin [3 ]
Wang, Nan [1 ,6 ]
Ma, Shengchao [1 ,6 ,7 ]
Nie, Lihong [5 ]
Jiang, Yideng [1 ,6 ,7 ]
机构
[1] Ningxia Med Univ, Sch Basic Med Sci, Dept Pathol & Pathophysiol, 1160 Shengli St, Yinchuan 750004, Ningxia, Peoples R China
[2] Ningxia Med Univ, Prenatal Diag Ctr, Gen Hosp, Yinchuan, Peoples R China
[3] Ningxia Med Univ, Sch Basic Med Sci, Dept Pathogen Biol & Immunol, Yinchuan, Peoples R China
[4] Ningxia Med Univ, Coll Pharm, Yinchuan, Peoples R China
[5] Ningxia Med Univ, Sch Basic Med Sci, Dept Physiol, Yinchuan, Peoples R China
[6] Ningxia Key Lab Vasc Injury & Repair Res, Yinchuan, Peoples R China
[7] NingXia Med Univ, NHC Key Lab Metab Cardiovasc Dis Res, Yinchuan, Peoples R China
基金
中国国家自然科学基金;
关键词
Atherosclerosis; Homocysteine; SCARB1; DNMT3b; SP1; DNA METHYLATION; SR-BI; CHOLESTEROL; EXPRESSION; INFLAMMATION; PROMOTER; CELLS; DNMT1; ABCA1; MIR-148A/152;
D O I
10.1016/j.yjmcc.2019.11.145
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Homocysteine (Hcy) is an independent risk factor for atherosclerosis, which is characterized by lipid accumulation in the atherosclerotic plaque. Increasing evidence supports that as the main receptor of high-density lipoprotein, scavenger receptor class B member 1 (SCARB1) is protective against atherosclerosis. However, the underlying mechanism regarding it in Hcy-mediated atherosclerosis remains unclear. Here, we found the remarkable inhibition of SCARB1 expression in atherosclerotic plaque and Hcy-treated foam cells, whereas overexpression of SCARB1 can suppress lipid accumulation in foam cells following Hcy treatment. Analysis of SCARB1 promoter showed that no significant change of methylation level was observed both in vivo and in vitro under Hcy treatment. Moreover, it was found that the negative regulation of DNMT3b on SCARB1 was due to the decreased recruitment of SP1 to SCARB1 promoter. Thus, we concluded that inhibition of SCARB1 expression induced by DNMT3b at least partly accelerated Hcy-mediated atherosclerosis through promoting lipid accumulation in foam cells, which was attributed to the decreased binding of SP1 to SCARB1 promoter. In our point, these findings will provide novel insight into an epigenetic mechanism for atherosclerosis.
引用
收藏
页码:34 / 48
页数:15
相关论文
共 49 条
[1]   A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells [J].
Ajiro, Masahiko ;
Jia, Rong ;
Yang, Yanqin ;
Zhu, Jun ;
Zheng, Zhi-Ming .
NUCLEIC ACIDS RESEARCH, 2016, 44 (04) :1854-1870
[2]  
[Anonymous], DEV CAMBRIDGE ENGLAN
[3]   Inflammation and beyond: new directions and emerging drugs for treating atherosclerosis [J].
Bertrand, Marie-Jeanne ;
Tardif, Jean-Claude .
EXPERT OPINION ON EMERGING DRUGS, 2017, 22 (01) :1-26
[4]   miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine [J].
Cao, ChengJian ;
Zhang, HuiPing ;
Zhao, Li ;
Zhou, Longxia ;
Zhang, Minghao ;
Xu, Hua ;
Han, Xuebo ;
Li, Guizhong ;
Yang, Xiaoling ;
Jiang, YiDeng .
EXPERIMENTAL CELL RESEARCH, 2016, 347 (01) :95-104
[5]   DNA Demethylation by DNMT3A and DNMT3B in vitro and of Methylated Episomal DNA in Transiently Transfected Cells [J].
Chatterjee, Biswanath ;
Lin, Miao-Hsia ;
Chen, Chun-Chang ;
Peng, Kai-Lin ;
Wu, Mu-Sheng ;
Tseng, Mei-Chun ;
Chen, Yu-Ju ;
Shen, Che-Kun James .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2018, 1861 (11) :1048-1061
[6]   The TGF-β-induced up-regulation of NKG2DLs requires AKT/GSK-3β-mediated stabilization of SP1 [J].
Chen, Xiao-Hui ;
Lu, Lin-lin ;
Ke, Hong-Peng ;
Liu, Zong-Cai ;
Wang, Hai-Fang ;
Wei, Wei ;
Qi, Yi-Fei ;
Wang, Hong-Sheng ;
Cai, Shao-Hui ;
Du, Jun .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2017, 21 (05) :860-870
[7]   Macrophage-mediated cholesterol handling in atherosclerosis [J].
Chistiakov, Dimitry A. ;
Bobryshev, Yuri V. ;
Orekhov, Alexander N. .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2016, 20 (01) :17-28
[8]   Non-catalytic functions of DNMT1 [J].
Espada, Jesus .
EPIGENETICS, 2012, 7 (02) :115-118
[9]   Hyperhomocysteinemia Potentiates Hyperglycemia-Induced Inflammatory Monocyte Differentiation and Atherosclerosis [J].
Fang, Pu ;
Zhang, Daqing ;
Cheng, Zhongjian ;
Yan, Chenghui ;
Jiang, Xiaohua ;
Kruger, Warren D. ;
Meng, Shu ;
Arning, Erland ;
Bottiglieri, Teodoro ;
Choi, Eric T. ;
Han, Yaling ;
Yang, Xiao-feng ;
Wang, Hong .
DIABETES, 2014, 63 (12) :4275-4290
[10]   Scavenger receptor B1 (SR-B1) profoundly excludes high density lipoprotein (HDL) apolipoprotein AII as it nibbles HDL-cholesteryl ester [J].
Gillard, Baiba K. ;
Bassett, G. Randall ;
Gotto, Antonio M., Jr. ;
Rosales, Corina ;
Pownall, Henry J. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292 (21) :8864-8873