title: Angiotensin-(1-7) upregulates expression of adenosine triphosphate-binding cassette transporter A1 and adenosine triphosphate-binding cassette transporter G1 through the Mas receptor through the liver X receptor alpha signalling pathway in THP-1 macrophages treated with angiotensin-II.
abstract: Adenosine triphosphate-binding cassette transporter A1 (ABCA1) and ABCG1 play crucial roles in reverse cholesterol transport, and have anti-atherosclerosis effects, and liver X receptor alpha (LXRα) can stimulate cholesterol efflux through these transporters. Angiotensin (Ang)-(1-7) can protect endothelial cells, inhibit smooth muscle cell growth, ameliorate inflammation and exert anti-atherosclerotic effects. In the present study, we attempted to clarify the effect of Ang-(1-7) on expression of ABCA1 and ABCG1, and explored the role of LXRα in the regulation of ABCA1 and ABCG1 in THP-1 macrophages that had been incubated with angiotensin-II (AngII). Ang-(1-7) increased ABCA1 and ABCG1 expression in a concentration-dependent manner at both the mRNA and protein levels, promoted cholesterol efflux, and decreased cholesterol content in THP-1 macrophages treated with AngII. Furthermore, Ang-(1-7) upregulated the expression of LXRα in a concentration-dependent manner in these cells. LXRα small interfering RNA, as well as the Mas receptor antagonist A-779, completely abolished these effects of Ang-(1-7). In summary, Ang-(1-7) upregulates ABCA1 and ABCG1 expression in THP-1 macrophages treated with AngII through the Mas receptor, via the LXRα pathway. This novel insight into the molecular mechanism underlying Ang-(1-7) and AngII interaction could prove useful for developing new strategies for treatment of cardiovascular diseases.
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Bian
authors.forename: Huiyu
authors.initials: H
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Bai
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Yang
authors.forename: Chuanshi
authors.initials: C
authors.lastname: Xiao
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000803:Angiotensin I / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000071518:Liver X Receptors; D026901:Membrane Transport Proteins; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D002784:Cholesterol; C118790:angiotensin I (1-7)
keywords: adenosine triphosphate-binding cassette transporter A1; adenosine triphosphate-binding cassette transporter G1; angiotensin-(1-7); liver X receptor α; reverse cholesterol transport