CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3β/β-cateninT120/TCF21 pathway

CXC chemokine ligand 12 (CXCL12) is a member of the CXC chemokine family and mainly acts on cell chemotaxis. CXCL12 also elicits a proatherogenic role, but the molecular mechanisms have not been fully defined yet. We aimed to reveal if and how CXCL12 promoted atherosclerosis via regulating lipid metabolism. In vitro, our data showed that CXCL12 could reduce ABCA1 expression, and it mediated cholesterol efflux from THP-1-derived macrophages to apoA-I. Data from the luciferase reporter gene and chromatin immunoprecipitation assays revealed that transcription factor 21 (TCF21) stimulated the transcription of ABCA1 via binding to its promoter region, which was repressed by CXCL12. We found that CXCL12 increased the levels of phosphorylated glycogen synthase kinase 3β (GSK3β) and the phosphorylation of β-catenin at the Thr120 position. Inactivation of GSK3β or β-catenin increased the expression of TCF21 and ABCA1. Further, knockdown or inhibition of CXC chemokine receptor 4 (CXCR4) blocked the effects of CXCL12 on TCF21 and ABCA1 expression and the phosphorylation of GSK3β and β-catenin. In vivo, the overexpression of CXCL12 in Apoe−/− mice via lentivirus enlarged the atherosclerotic lesion area and increased macrophage infiltration in atherosclerotic plaques. We further found that the overexpression of CXCL12 reduced the efficiency of reverse cholesterol transport and plasma HDL-C levels, decreased ABCA1 expression in the aorta and mouse peritoneal macrophages (MPMs), and suppressed cholesterol efflux from MPMs to apoA-I in Apoe−/− mice. Collectively, these findings suggest that CXCL12 interacts with CXCR4 and then activates the GSK-3β/β-cateninT120/TCF21 signaling pathway to inhibit ABCA1-dependent cholesterol efflux from macrophages and aggravate atherosclerosis. Targeting CXCL12 may be a novel and promising strategy for the prevention and treatment of atherosclerotic cardiovascular diseases. CXC chemokine ligand 12 (CXCL12) is a member of the CXC chemokine family and mainly acts on cell chemotaxis. CXCL12 also elicits a proatherogenic role, but the molecular mechanisms have not been fully defined yet. We aimed to reveal if and how CXCL12 promoted atherosclerosis via regulating lipid metabolism. In vitro, our data showed that CXCL12 could reduce ABCA1 expression, and it mediated cholesterol efflux from THP-1-derived macrophages to apoA-I. Data from the luciferase reporter gene and chromatin immunoprecipitation assays revealed that transcription factor 21 (TCF21) stimulated the transcription of ABCA1 via binding to its promoter region, which was repressed by CXCL12. We found that CXCL12 increased the levels of phosphorylated glycogen synthase kinase 3β (GSK3β) and the phosphorylation of β-catenin at the Thr120 position. Inactivation of GSK3β or β-catenin increased the expression of TCF21 and ABCA1. Further, knockdown or inhibition of CXC chemokine receptor 4 (CXCR4) blocked the effects of CXCL12 on TCF21 and ABCA1 expression and the phosphorylation of GSK3β and β-catenin. In vivo, the overexpression of CXCL12 in Apoe−/− mice via lentivirus enlarged the atherosclerotic lesion area and increased macrophage infiltration in atherosclerotic plaques. We further found that the overexpression of CXCL12 reduced the efficiency of reverse cholesterol transport and plasma HDL-C levels, decreased ABCA1 expression in the aorta and mouse peritoneal macrophages (MPMs), and suppressed cholesterol efflux from MPMs to apoA-I in Apoe−/− mice. Collectively, these findings suggest that CXCL12 interacts with CXCR4 and then activates the GSK-3β/β-cateninT120/TCF21 signaling pathway to inhibit ABCA1-dependent cholesterol efflux from macrophages and aggravate atherosclerosis. Targeting CXCL12 may be a novel and promising strategy for the prevention and treatment of atherosclerotic cardiovascular diseases. Atherosclerosis is a chronic vascular disease that has been identified as one of the pathogenesis of cardiovascular disease. It is well known that atherosclerosis is driven by the dysregulation of cholesterol metabolism, leading to the formation of foam cells, a hallmark of atherosclerosis (1.Yu X.H. Zhang D.W. Zheng X.L. Tang C.K. C1q tumor necrosis factor-related protein 9 in atherosclerosis: mechanistic insights and therapeutic potential.Atherosclerosis. 2018; 276: 109-116Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar). Reverse cholesterol transport (RCT) is an important approach in preventing lipid accumulation during atherogenesis (2.Marques L.R. Diniz T.A. Antunes B.M. Rossi F.E. Caperuto E.C. Lira F.S. Gonçalves D.C. Reverse cholesterol transport: molecular mechanisms and the non-medical approach to enhance HDL cholesterol.Front. Physiol. 2018; 9: 526-537Crossref PubMed Scopus (70) Google Scholar, 3.Yu X.H. Zhang D.W. Zheng X.L. Tang C.K. Cholesterol transport system: an integrated cholesterol transport model involved in atherosclerosis.Prog. Lipid Res. 2019; 73: 65-91Crossref PubMed Scopus (120) Google Scholar). ABCA1 locates in the plasma membrane, serving as a cholesterol transporter to mediate excessive cholesterol efflux from macrophages to apoA-I. This is believed to be the first and most important step of RCT. Indeed, several lines of evidence have demonstrated that ABCA1 expression and cholesterol efflux are inversely associated with the development and progression of atherosclerosis (4.Gao J.H. Zeng M.Y. Yu X.H. Zeng G.F. He L.H. Zheng X.L. Zhang D.W. Ouyang X.P. Tang C.K. Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-κB/miR-33a pathway in THP-1 macrophage-derived foam cells.Biochem. Biophys. Res. Commun. 2018; 500: 318-324Crossref PubMed Scopus (16) Google Scholar, 5.Zhang M. Li L. Xie W. Wu J.F. Yao F. Tan Y.L. Xia X.D. Liu X.Y. Liu D. Lan G. Apolipoprotein A-1 binding protein promotes macrophage cholesterol efflux by facilitating apolipoprotein A-1 binding to ABCA1 and preventing ABCA1 degradation.Atherosclerosis. 2016; 248: 149-159Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 6.Zhang M. Zhao G.J. Yin K. Xia X.D. Gong D. Zhao Z.W. Chen L.Y. Zheng X.L. Tang X.E. Tang C.K. Apolipoprotein A-1 binding protein inhibits inflammatory signaling pathways by binding to apolipoprotein A-1 in THP-1 macrophages.Circ. J. 2018; 82: 1396-1404Crossref PubMed Scopus (29) Google Scholar, 7.Zhao Z.W. Zhang M. Chen L.Y. Gong D. Xia X.D. Yu X.H. Wang S.Q. Ou X. Dai X.Y. Zheng X.L. Heat shock protein 70 accelerates atherosclerosis by downregulating the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.Biochim Biophys Acta Mol Cell Biol Lipids. 2018; 1863: 806-822Crossref PubMed Scopus (32) Google Scholar). Thus, understanding how ABCA1 expression is regulated has always been an important research topic. Chemokines are a group of molecules that mainly function on cell chemotaxis and are extensively expressed in vascular cells, such as macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs). CXC chemokine ligand 12 (CXCL12) belongs to the CXC subclass of the chemokine family. Several clinical reports have shown that higher serum levels of CXCL12 are closely related to an increase in atherosclerotic risk (8.Mehta N.N. Li M. William D. Khera A.V. DerOhannessian S. Qu L. Ferguson J.F. McLaughlin C. Shaikh L.H. Shah R. et al.The novel atherosclerosis locus at 10q11 regulates plasma CXCL12 levels.Eur. Heart J. 2011; 32: 963-971Crossref PubMed Scopus (59) Google Scholar, 9.Camnitz W. Burdick M.D. Strieter R.M. Mehrad B. Keeley E.C. Dose-dependent effect of statin therapy on circulating CXCL12 levels in patients with hyperlipidemia.Clin. Transl. Med. 2012; 1: 23-28Crossref PubMed Google Scholar, 10.Farouk S.S. Rader D.J. Reilly M.P. Mehta N.N. CXCL12: a new player in coronary disease identified through human genetics.Trends Med. PubMed Scopus Google Scholar, M. G. M. R. and CXCL12 chemokine levels are associated with the of coronary disease and coronary J. Full Text Full Text PDF PubMed Scopus Google Scholar). overexpression of CXCL12 aggravate atherosclerosis progression in Apoe−/− mice S. M. C. of in formation vascular in apolipoprotein PubMed Scopus Google Scholar, Yu Tang CXC chemokine ligand 12 (CXCL12) in atherosclerosis: an therapeutic 2019; PubMed Scopus (24) Google Scholar). CXC chemokine receptor 4 a receptor for is with lesion and risk for cardiovascular disease D. G. S. molecular of chemokine receptor CXCR4 expression in atherosclerotic with cardiovascular risk and Med. 2018; PubMed Scopus Google Scholar, B. M. C. is in and of smooth muscle Res. PubMed Scopus Google Scholar, Li L. G. Li X. M. Xie L. S. et al.The in apolipoprotein J. PubMed Scopus Google Scholar). et S. M. C. R. J. G. M. C. and of CXCR4 and CXCL12 in human atherosclerotic 2018; PubMed Scopus Google that CXCL12 and CXCR4 expressed in macrophages human atherosclerosis. It has been shown that CXCL12 the formation of macrophage-derived foam cells via CXCR4 M. F. M. S. M. CXCL12 regulates macrophages and foam cells through of PubMed Scopus Google Scholar). the of CXCL12 in cholesterol efflux is synthase kinase 3β (GSK3β) is a kinase that is involved in synthase kinase an therapeutic Med. Full Text Full Text PDF PubMed Scopus Google Scholar). and knockdown of GSK3β and inhibit and glycogen synthase in apolipoprotein mouse of 2012; 32: PubMed Scopus Google Scholar, D.J. Atherosclerosis by a is by via of expression in PubMed Scopus Google Scholar). GSK3β has been in during the of GSK3β in cholesterol efflux has to be β-catenin belongs to the family and acts as a to the transcription of is G. K. and of J. 2012; PubMed Scopus Google Scholar). in protein phosphorylation regulates the of β-catenin from the to the and the This has been in the development of cardiovascular disease Li Wang Chen Chen L. Zheng C. Wang W. et and in mice by the of Res. 2019; of Google Scholar, B. Wang J. W. Wang X. J. et a novel 4 through of the signaling 2019; PubMed Scopus Google Scholar, M. S. pathway through inhibition and Full Text Full Text PDF PubMed Scopus Google Scholar). factor 21 (TCF21) is a member of the transcription factor family and the development of coronary R. R. of a factor expressed in cells of the and the coronary 73: PubMed Scopus Google Scholar). et X. W. C. S. C. in new for coronary 2012; PubMed Scopus Google found that TCF21 was associated with the risk of coronary disease in a inhibition of TCF21 expression risk D. in TCF21 a binding and PubMed Scopus Google Scholar). the mechanisms to be In found that the binding of CXCL12 to CXCR4 the This ABCA1 expression and reduced cholesterol Further, our data the proatherogenic of CXCL12 in Apoe−/− mice. Apoe−/− mice from a from Apoe−/− mice with of or via the and then the for 12 mice and to mice with by an of for the of peritoneal in with the and the of for the of from mice with of lesion and is in with and and D. G. R. on and of atherosclerosis a from the Heart PubMed Scopus Google Scholar, M. Zhao G.J. Yao F. Xia X.D. Gong D. Zhao Z.W. Chen L.Y. Zheng X.L. Tang X.E. Tang C.K. atherosclerosis by reverse cholesterol transport and in 2018; Full Text Full Text PDF PubMed Scopus Google Scholar). then the with and with a to the of atherosclerotic on the to the of the aorta the was identified by the of of We from mouse group for and lesion with and the with lipid levels as Z.W. Zhang M. Chen L.Y. Gong D. Xia X.D. Yu X.H. Wang S.Q. Ou X. Dai X.Y. Zheng X.L. Heat shock protein 70 accelerates atherosclerosis by downregulating the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.Biochim Biophys Acta Mol Cell Biol Lipids. 2018; 1863: 806-822Crossref PubMed Scopus (32) Google Scholar). from the of Apoe−/− mice with or or and the for 12 levels of cholesterol and levels by and of with and blocked with serum for at THP-1-derived macrophages with or with and then with the and cells with or at by for at in a with of ABCA1 and in the and ABCA1 and CXCR4 in cells an on the of and cells aorta with serum for and then with mouse in a at with a for at by for then with for with a and then with for with for an efficiency of was as Z.W. Zhang M. Chen L.Y. Gong D. Xia X.D. Yu X.H. Wang S.Q. Ou X. Dai X.Y. Zheng X.L. Heat shock protein 70 accelerates atherosclerosis by downregulating the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.Biochim Biophys Acta Mol Cell Biol Lipids. 2018; 1863: 806-822Crossref PubMed Scopus (32) Google Scholar). macrophages with and for in cells the of mice. was at and from to the of the and in for was from in with and at was and at a of with for the for the of and was with a as the of or THP-1 from the of cell and in with and cells from the of cell and in at in a of of THP-1 macrophages was by for THP-1-derived macrophages and cells in for β-catenin GSK3β inhibitor CXCR4 inhibitor or human CXCL12 protein was with CXCR4 and TCF21 to cells by and to 12 the was to and and by the and with a and protein was as the for from and cells and was as the for B. He J. Liu X. Zhang C. D. regulates phosphorylation to endothelial to 2019; PubMed Scopus Google Scholar). and to by and binding was with a and THP-1-derived macrophages with CXCL12 and then and in was in with at by an with protein at then in from the with at for and then to Cholesterol efflux was as (4.Gao J.H. Zeng M.Y. Yu X.H. Zeng G.F. He L.H. Zheng X.L. Zhang D.W. Ouyang X.P. Tang C.K. Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-κB/miR-33a pathway in THP-1 macrophage-derived foam cells.Biochem. Biophys. Res. Commun. 2018; 500: 318-324Crossref PubMed Scopus (16) Google Scholar). THP-1-derived macrophages with or CXCL12 for 12 and then in and for macrophages from Apoe−/− mice and in for peritoneal macrophages and THP-1-derived macrophages with and then with for in the cells in and then in and apoA-I or HDL for in and cells was in a Cholesterol efflux was as the of in to in cells and lipid in THP-1-derived macrophages was as (4.Gao J.H. Zeng M.Y. Yu X.H. Zeng G.F. He L.H. Zheng X.L. Zhang D.W. Ouyang X.P. Tang C.K. Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-κB/miR-33a pathway in THP-1 macrophage-derived foam cells.Biochem. Biophys. Res. Commun. 2018; 500: 318-324Crossref PubMed Scopus (16) Google Scholar). THP-1-derived macrophages with cells in on the the protein was to cholesterol and then at was as cholesterol and then with and to cholesterol cholesterol in was to cholesterol or cholesterol with cholesterol for the of at for was then by for at for at of was to a for at was with cholesterol by the THP-1-derived macrophages, and for of the as human and human and and mouse and levels with an TCF21 expression was from luciferase with the promoter of of the human ABCA1 by cells with CXCL12 or with TCF21 overexpression cells then with of the ABCA1 promoter reporter and luciferase reporter 12 cells in and in and luciferase was the in the luciferase and as a of the THP-1-derived macrophages with CXCL12 in for at was by and then to the cells with an for of with 9 on the Cell at for at chromatin was on the to immunoprecipitation a chromatin immunoprecipitation and TCF21 or was and for of human ABCA1 data are as of data was by an and showed was by or was for the was for the was for was the of CXCL12 in lipid metabolism, THP-1-derived macrophages with CXCL12. shown in CXCL12 reduced the and protein levels of ABCA1. ABCA1 in THP-1-derived macrophages ABCA1 was reduced in cells the important of ABCA1 in the of cholesterol cholesterol efflux apoA-I and and found that CXCL12 reduced cholesterol efflux to apoA-I but not CXCL12 increased the of and in THP-1-derived macrophages these findings that CXCL12 an effect on cholesterol efflux from THP-1-derived macrophages via the of ABCA1 effect of CXCL12 on the lipid of THP-1-derived of the levels of and data are shown as from in the in a new of the levels of and data are shown as from in the TCF21 to the promoter of its and regulates its We the promoter of ABCA1 in to TCF21 and CXCL12 in cells the luciferase and found that TCF21 CXCL12 decreased ABCA1 promoter from the chromatin immunoprecipitation that CXCL12 the binding of TCF21 to ABCA1 in THP-1-derived macrophages the effect of CXCL12 on TCF21 and ABCA1 expression in THP-1-derived shown in and CXCL12 decreased the and protein levels of TCF21 and the of ABCA1 suggest that CXCL12 inhibits TCF21 expression, ABCA1 transcription and downregulating its that β-catenin regulates the of family that β-catenin as an for the expression of ABCA1. the protein levels of β-catenin in THP-1-derived and as the for and that the treatment of CXCL12 decreased the of β-catenin but increased β-catenin the expression of TCF21 and ABCA1 by the β-catenin the of β-catenin is regulated by its phosphorylated β-catenin that phosphorylation at Thr120 and shown in CXCL12 increased levels of but not that the phosphorylation of GSK3β reduced the of GSK3β to ABCA1 Indeed, CXCL12 increased the of the GSK3β inhibitor blocked of β-catenin and the levels of phosphorylated In the expression of TCF21 and ABCA1 these data suggest that the pathway acts as the for the effect of CXCL12 on the expression of TCF21 and was for the phosphorylation of β-catenin by CXCL12. THP-1-derived macrophages with CXCL12 of phosphorylation levels of GSK3β of and β-catenin of the levels of phosphorylated and of and protein levels of TCF21 or ABCA1 and data are shown as from in the the CXCR4 is a receptor for CXCL12 and We and that CXCL12 with CXCR4 in THP-1 macrophages the knockdown efficiency of CXCR4 the protein levels and of CXCR4 in THP-1-derived macrophages and shown in and the expression and of CXCR4 reduced in THP-1-derived macrophages with CXCR4 In found that the effect of CXCL12 on the phosphorylation of GSK3β was blocked by the knockdown of CXCR4 and the CXCR4 inhibitor We then and and as a protein for the and to a B. He J. Liu X. Zhang C. D. regulates phosphorylation to endothelial to 2019; PubMed Scopus Google Scholar). We that the inhibition of CXCR4 suppressed the increase in the of β-catenin and the levels of the inhibition of CXCR4 also suppressed the in the and protein levels of TCF21 and ABCA1 these findings that the binding of CXCL12 to CXCR4 is for the of the leading to the of ABCA1 the of CXCL12 in atherosclerotic in and the of Apoe−/− mice. We first plasma levels of CXCL12 in Apoe−/− mice and found that CXCL12 was increased in Apoe−/− mice with shown in and CXCL12 increased the of and also revealed that a area in the was increased in the in a lesion area of mice not with the and CXCL12 is a of cell its effect on macrophage infiltration atherosclerotic and CXCL12 increased the of macrophages in atherosclerotic with the and the effect of CXCL12 on lipid metabolism, the plasma lipid of Apoe−/− mice and found that HDL-C was reduced in the CXCL12 was in and Collectively, our data that CXCL12 plasma HDL levels and promotes the formation of atherosclerotic in Apoe−/− of CXCL12 in the of plasma lipid levels in a of and in Apoe−/− mice by data are shown as from in the in a new of and in Apoe−/− mice by data are shown as from in the the levels of ABCA1 in the and MPMs of Apoe−/− mice and found an effect of CXCL12 on ABCA1 expression from further revealed that the of ABCA1 reduced in the of Apoe−/− mice CXCL12 found that CXCL12 reduced cholesterol efflux from MPMs to apoA-I and an effect on the efficiency of to the and in Apoe−/− mice data suggest that CXCL12 ABCA1 expression and then inhibits the development of and macrophages the of Apoe−/− mice with lentivirus or and the of the of in serum the and data are shown as mice the model for cholesterol efflux in CXCL12 promotes phosphorylation of GSK3β and β-catenin This the expression of TCF21 and macrophage cholesterol Thus, CXCL12 a effect on We found for the first that CXCL12 reduced the expression of ABCA1 and cholesterol efflux from macrophages to apoA-I. CXCL12 CXCR4 and the expression of the promoter of ABCA1. In our findings revealed that the of the pathway as the for the in TCF21 expression and that CXCL12 promoted the development of atherosclerotic in Apoe−/− mice. evidence that CXCL12 cardiovascular atherosclerosis S.S. Rader D.J. Reilly M.P. Mehta N.N. CXCL12: a new player in coronary disease identified through human genetics.Trends Med. PubMed Scopus Google Scholar, Yu Tang CXC chemokine ligand 12 (CXCL12) in atherosclerosis: an therapeutic 2019; PubMed Scopus (24) Google Scholar, N.N. G.J. Shah R. C. M. Chen J. M. plasma CXCL12 levels and in chronic findings from the Heart J. PubMed Scopus Google Scholar, D.J. M. L. C. factor cardiovascular in patients with coronary Full Text Full Text PDF PubMed Scopus Google Scholar). in on the proatherogenic of CXCL12 by the and of atherosclerotic S. M. C. of in formation vascular in apolipoprotein PubMed Scopus Google Scholar). defined the mechanisms of CXCL12 in is the leading of atherosclerosis. et M. F. M. S. M. CXCL12 regulates macrophages and foam cells through of PubMed Scopus Google that CXCL12 the of macrophages foam that CXCL12 lipid in the first showed that CXCL12 reduced ABCA1 expression and cholesterol efflux from macrophages to apoA-I. ABCA1 mainly the efflux of cholesterol ABCG1 mainly cholesterol efflux HDL M. X. D. of apoA-I and with ABCA1 reveal mechanisms of HDL Lipid Res. 2019; Full Text Full Text PDF PubMed Scopus (16) Google Scholar, K. Yin L. Zhang protein regulates expression, cholesterol and 2019; PubMed Scopus Google Scholar, C. X. Li L. B. Chen S. Wang L. X. D. regulates ABCG1 expression and cholesterol efflux from vascular smooth muscle cells through a 2019; Full Text Full Text PDF PubMed Scopus Google Scholar, K. S. M. D. J. et of cholesterol efflux with coronary lipid by 2019; 9: PubMed Scopus Google Scholar). the in cholesterol efflux to apoA-I but not to HDL that CXCL12 cholesterol efflux by downregulating ABCA1 of in THP-1-derived macrophages also evidence to lipid the receptor of is expressed in atherosclerotic and acts as an important of macrophage the of atherosclerotic D. G. S. molecular of chemokine receptor CXCR4 expression in atherosclerotic with cardiovascular risk and Med. 2018; PubMed Scopus Google Scholar, K. Li X. K. C. CXCR4 is as in formation 2012; PubMed Scopus Google Scholar). We a novel of cholesterol efflux from macrophages via binding to CXCL12. the overexpression of CXCL12 in Apoe−/− mice to a in plasma HDL-C levels, which is to the of ABCA1 inhibition of ABCA1 expression and cholesterol efflux from MPMs in Apoe−/− mice the for the in plasma HDL-C HDL a in that promotes the transport of cholesterol from cells to the for G.F. Rader D.J. insights the of HDL and reverse cholesterol Res. PubMed Scopus Google Scholar). the effect of CXCL12 on lipid metabolism, efficiency in Apoe−/− mice and found that the overexpression of CXCL12 reduced RCT. our data suggest that CXCL12 lipid by cholesterol atherosclerosis. et J. S. K. D. D. Rader D.J. D. et from endothelial cells promotes atherosclerosis to coronary 2019; PubMed Scopus Google that CXCL12 to plasma CXCL12 levels and is an for data that the overexpression of CXCL12 in Apoe−/− mice the development of atherosclerosis. We also found that the of macrophages with CXCL12 to a in cholesterol efflux and a of lipid of CXCL12 in macrophages plasma CXCL12 levels and the and progression of atherosclerosis to be in the It has been that CXCL12 treatment has effect on macrophage in Apoe−/− mice. of CXCL12 in or also has effect on macrophage in atherosclerotic J. S. K. D. D. Rader D.J. D. et from endothelial cells promotes atherosclerosis to coronary 2019; PubMed Scopus Google Scholar, C. of smooth muscle foam cell formation in 2019; PubMed Scopus Google Scholar). our revealed that the overexpression of CXCL12 increased macrophage infiltration atherosclerotic of Apoe−/− mice. This may that macrophage-derived CXCL12 could as an for macrophage showed that of CXCL12 in Apoe−/− mice to a in the lesion area and the of CXCL12 in the of C. of smooth muscle foam cell formation in 2019; PubMed Scopus Google Scholar). the that are involved in the of atherosclerotic and atherosclerosis progression C. of smooth muscle foam cell formation in 2019; PubMed Scopus Google the effect of CXCL12 on be in our TCF21 has been in and in M. K. R. S. F. M. S. et of a transcription factor 21 gene with PubMed Scopus Google Scholar, M. M.D. R. in and TCF21 are associated with increased to coronary disease in an 2016; PubMed Scopus Google Scholar, R. K. Chen et factor and signaling pathways an of TCF21 expression at the coronary disease 9: PubMed Scopus Google Scholar). et K. R. K. et disease associated transcription factor TCF21 regulates smooth muscle cells that to the PubMed Scopus Google that TCF21 was involved in the progression of atherosclerotic et D. Zhao R. Liu B. M. et disease and TCF21 that smooth muscle cell and disease 2018; PubMed Scopus Google identified TCF21 as an is known the by which TCF21 regulates In our findings suggest that TCF21 an by ABCA1 expression, which may a novel of TCF21 in cardiovascular disease. In found that TCF21 increased ABCA1 promoter but CXCL12 an This an of CXCL12 with showed that CXCL12 the binding of TCF21 to the ABCA1 promoter by downregulating TCF21 In the inhibition of CXCR4 the effect of CXCL12 on the expression of TCF21 and ABCA1. the effect of the on cholesterol efflux may on a member of the signaling is the by the of family X. Zhao for the factor signaling in vascular Res. PubMed Scopus Google Scholar). pathway is by as a R. B. and promotes lipid infiltration in Med. PubMed Scopus Google Scholar). Chen et Zheng W. Wang J. Chen X. regulates expression via Biophys. Res. Commun. 2018; PubMed Scopus Google Scholar, L.R. K. of vascular smooth muscle receptor inhibits signaling and in Res. PubMed Scopus Google that β-catenin the of by We found for the first that the has an effect on β-catenin leading to the of TCF21 and ABCA1 expression in THP-1-derived GSK3β elicits a effect on the pathway and is closely related to atherosclerosis. and kinase kinase and glycogen synthase foam cell Lipid Res. Full Text Full Text PDF PubMed Scopus (24) Google found that GSK3β atherosclerotic and formation in Apoe−/− mice. of a GSK3β inhibitor lipid accumulation Wu Chen et and are for lipid by in 2011; PubMed Scopus Google Scholar). We found that GSK3β cholesterol efflux and then promoted which on β-catenin. It has been that the phosphorylation of β-catenin regulates the of β-catenin the and Li Wang Chen Chen L. Zheng C. Wang W. et and in mice by the of Res. 2019; of Google Scholar, B. Wang J. W. Wang X. J. et a novel 4 through of the signaling 2019; PubMed Scopus Google Scholar, F. Chen W. Liu W. J. Zhang X. Yin X. inhibits in via and protein kinase but not kinase Physiol. 2018; PubMed Scopus (16) Google Scholar, M. S. pathway through inhibition and Full Text Full Text PDF PubMed Scopus Google Scholar). further the phosphorylation of β-catenin and found that phosphorylation at Thr120 in β-catenin by GSK3β was for TCF21 and ABCA1 et C. Zhang C. Li phosphorylated at of by in 2012; PubMed Scopus Google that β-catenin was by phosphorylation at with our that CXCL12 increased β-catenin our findings reveal for the first that CXCL12 accelerates atherosclerosis via the of ABCA1 expression and then the of cholesterol efflux from In the binding of CXCL12 to CXCR4 is for the of the signaling pathway and of TCF21 expression CXCL12 be a promising for atherosclerosis. coronary disease CXC chemokine ligand 12 CXC chemokine receptor 4 endothelial cell glycogen synthase kinase 3β mouse peritoneal macrophage reverse cholesterol transport vascular smooth muscle cell cholesterol transcription factor transcription factor 21

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.