Your browser doesn't support javascript.
loading
LncRNA ENST00000602558.1 regulates ABCG1 expression and cholesterol efflux from vascular smooth muscle cells through a p65-dependent pathway.
Cai, Can; Zhu, Huijuan; Ning, Xiaotong; Li, Lin; Yang, Bin; Chen, Shufeng; Wang, Laiyuan; Lu, Xiangfeng; Gu, Dongfeng.
Afiliação
  • Cai C; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
  • Zhu H; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
  • Ning X; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
  • Li L; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
  • Yang B; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
  • Chen S; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
  • Wang L; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
  • Lu X; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
  • Gu D; Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China.
Atherosclerosis ; 285: 31-39, 2019 06.
Article em En | MEDLINE | ID: mdl-31003090
ABSTRACT
BACKGROUND AND

AIMS:

Long non-coding RNAs (lncRNAs) have proven to be involved in the progression of atherosclerosis and dyslipidemia. In addition, vascular smooth muscle cells (VSMCs) phenotype switching, including VSMCs-derived foam cells formation, plays a key role in the pathogenesis of atherosclerosis. LncRNA ENST00000602558.1, one of the differentially expressed lncRNAs between coronary artery disease (CAD) patients and healthy controls identified by our previous study, was located to TG and HDL susceptibility loci, but its role and underlying mechanism in the pathogenesis of atherosclerosis remain unclear. The present study aims to explore the role and underlying mechanism of ENST00000602558.1 in the regulation of cholesterol efflux from VSMCs.

METHODS:

ABCG1 mRNA and protein expression in VSMCs was detected using qRT-PCR and Western blot, respectively. ABCG1-mediated cholesterol efflux to HDL from VSMCs was measured by means of NBD-cholesterol fluorescence intensity. The binding of ENST00000602558.1 to p65 and p65 to ABCG1 promoter region was detected by RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay, respectively.

RESULTS:

Overexpression of ENST00000602558.1 downregulated ABCG1 mRNA and protein expression, while knockdown of ENST00000602558.1 upregulated ABCG1 mRNA and protein expression. Consistently, ENST00000602558.1 overexpression decreased ABCG1-mediated cholesterol efflux to HDL from VSMCs by 30.38% (p < 0.001), and knockdown of ENST00000602558.1 increased ABCG1-mediated cholesterol efflux to HDL from VSMCs by 30.41% (p = 0.001). In addition to cholesterol efflux, overexpression of ENST00000602558.1 increased lipid accumulation and TC/TG levels, while knockdown of ENST00000602558.1 decreased lipid accumulation and TC/TG levels in VSMCs. Furthermore, we confirmed that ENST00000602558.1 regulated ABCG1 expression and ABCG1-mediated cholesterol efflux from VSMCs through binding to p65.

CONCLUSIONS:

In conclusion, ENST00000602558.1 played an important role in mediating cholesterol efflux to HDL from VSMCs by regulating ABCG1 expression through binding to p65.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colesterol / Miócitos de Músculo Liso / Fator de Transcrição RelA / RNA Longo não Codificante / Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP / Músculo Liso Vascular Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Atherosclerosis Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China País de publicação: IE / IRELAND / IRLANDA

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colesterol / Miócitos de Músculo Liso / Fator de Transcrição RelA / RNA Longo não Codificante / Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP / Músculo Liso Vascular Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Atherosclerosis Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China País de publicação: IE / IRELAND / IRLANDA