Received:11 September 2016,
Published:15 February 2017
移动端阅览
Fei Gao, Xiaolu Hu, Kangning Chen. Peroxisome proliferators-activated receptor-gamma agonist inhibits angiotensin Ⅱ -induced phenotypic switching of vascular smooth muscle cells[J]. Journal of Third Military Medical University, 2017, 39(3): 229-235.
Fei Gao, Xiaolu Hu, Kangning Chen. Peroxisome proliferators-activated receptor-gamma agonist inhibits angiotensin Ⅱ -induced phenotypic switching of vascular smooth muscle cells[J]. Journal of Third Military Medical University, 2017, 39(3): 229-235. DOI: 10.16016/j.1000-5404.201609078.
Objective
2
To investigate the inhibitory effect of peroxisome proliferator-activated receptor-gamma (PPAR-
γ
) agonist
rosiglitazone (RSG)
on the phenotypic switching in vascular smooth muscle cells (VSMCs) induced by angiotensin Ⅱ (AngⅡ).
Methods
2
AngⅡ was employed to induce phenotypic switching in cultured mouse VSMCs. After pretreated with RSG and then treated with AngⅡ
the migration of VSMCs was analyzed by Transwell chamber assay
and F-actin polymerization was detected by Phalloidine-iFluor
TM
488 staining under
a
laser confocal microscope. The protein and mRNA levels of PPAR-
γ
PKGⅠα and smooth muscle 22 alpha (SM22α
a
marker molecule in differentiated VSMC with contractile phenotype) were measured by Western blotting and RT-qPCR. Also
Western blotting was employed to detect protein levels of PKGⅠα and SM22α in the VSMCs which were pretreated with PPAR-
γ
inhibitor
GW9662 before RSG stimulation.
Results
2
RSG (20 μmol/L) pretreatment significantly inhibited AngⅡ-induced VSMCs immigration (
P
<
0.05) and formation of actin cytoskeleton. Results from RT-qPCR indicated that RSG pretreatment also reversed the down-regulation of PKGⅠα and SM22α at mRNA and protein levels in Ang Ⅱ-stimulated VSMCs (all
P
<
0.05). However
GW9662 treatment could attenuate the up-regulation of PKGⅠα and SM22α in RSG-treated VSMCs (
P
<
0.05).
Conclusion
2
RSG inhibits the phenotypic switching of VSMCs from
a
"contractile" to
a
"synthetic" state in response to Ang Ⅱ through activating PPAR-
γ
and then up-regulating PKGⅠα.
Ceriello A Thiazolidinediones as anti-inflammatory and anti-atherogenic agents Diabetes Metab Res Rev 2008 24 1 14 26 10.1002/dmrr.790 Ceriello A. Thiazolidinediones as anti-inflammatory and anti-atherogenic agents[J]. Diabetes Metab Res Rev, 2008, 24(1): 14-26.DOI: 10.1002/dmrr.790
Lagna G Ku M M Nguyen P H Control of phenotypic plasticity of smooth muscle cells by bone morphogenetic protein signaling through the myocardin-related transcription factors J Biol Chem 2007 282 51 37244 37255 10.1074/jbc.M708137200 Lagna G, Ku M M, Nguyen P H, et al . Control of phenotypic plasticity of smooth muscle cells by bone morphogenetic protein signaling through the myocardin-related transcription factors[J ] . J Biol Chem, 2007, 282(51): 37244-37255.DOI: 10.1074/jbc.M708137200
Lin G Chow S Lin J Effect of cell passage and density on protein kinase G expression and activation in vascular smooth muscle cells J Cell Biochem 2004 92 1 104 112 10.1002/jcb.20043 Lin G, Chow S, Lin J, et al . Effect of cell passage and density on protein kinase G expression and activation in vascular smooth muscle cells[J ] . J Cell Biochem, 2004, 92(1): 104-112. DOI: 10.1002/jcb.20043
Yoshida T Owens G K Molecular determinants of vascular smooth muscle cell diversity Circ Res 2005 96 3 280 291 10.1161/01.RES.0000155951.62152.2e Yoshida T, Owens G K. Molecular determinants of vascular smooth muscle cell diversity[J]. Circ Res, 2005, 96(3): 280-291.DOI: 10.1161/01.RES.0000155951.62152.2e
Zhang Z Wang M Fan X H Upregulation of TRPM7 channels by angiotensin Ⅱ triggers phenotypic switching of vascular smooth muscle cells of ascending aorta Circ Res 2012 111 9 1137 1146 10.1161/CIRCRESAHA.112.273755 Zhang Z, Wang M, Fan X H, et al . Upregulation of TRPM7 channels by angiotensin Ⅱ triggers phenotypic switching of vascular smooth muscle cells of ascending aorta[J ] . Circ Res, 2012, 111(9):1137-1146.DOI:10.1161/CIRCRESAHA.112.273755
Lim S Park S Erratum: Role of vascular smooth muscle cell in the inflammation of atherosclerosis BMB Rep 2016 49 2 134 https://www.researchgate.net/profile/Soyeon_Lim/publication/259586339_Role_of_vascular_smooth_muscle_cell_in_the_inflammation_of_atherosclerosis/links/53e02b2b0cf27a7b830a3756.pdf?origin=publication_detail Lim S, Park S. Erratum: Role of vascular smooth muscle cell in the inflammation of atherosclerosis[J]. BMB Rep, 2016, 49(2): 134.
Gao D Hao G Meng Z Rosiglitzone suppresses angiotensin Ⅱ-induced production of KLF5 and cell proliferation in rat vascular smooth muscle cells PLoS One 2015 10 4 e0123724 10.1371/journal.pone.0123724 Gao D, Hao G, Meng Z, et al . Rosiglitzone suppresses angiotensin Ⅱ-induced production of KLF5 and cell proliferation in rat vascular smooth muscle cells[J ] . PLoS One, 2015, 10(4):e0123724.DOI:10.1371/journal.pone.0123724
Iglarz M Touyz R M Amiri F Effect of peroxisome proliferator-activated receptor-alpha and -gamma activators on vascular remodeling in endothelin-dependent hypertension Arterioscler Thromb Vasc Biol 2003 23 1 45 51 10.1161/01.ATV.0000047447.67827.CD Iglarz M, Touyz R M, Amiri F, et al . Effect of peroxisome proliferator-activated receptor-alpha and -gamma activators on vascular remodeling in endothelin-dependent hypertension[J ] . Arterioscler Thromb Vasc Biol, 2003, 23(1): 45-51.DOI: 10.1161/01.ATV.0000047447.67827.CD
Silva-Junior Gde O Torres Tda S Mendonca Lde S Rosiglitazone (peroxisome proliferator-activated receptor-gamma) counters hypertension and adverse cardiac and vascular remodeling in 2K1C hypertensive rats Exp Toxicol Pathol 2011 63 1/2 1 7 10.1016/j.etp.2009.09.001 Silva-Junior Gde O, Torres Tda S, Mendonca Lde S, et al . Rosiglitazone (peroxisome proliferator-activated receptor-gamma) counters hypertension and adverse cardiac and vascular remodeling in 2K1C hypertensive rats[J ] . Exp Toxicol Pathol, 2011, 63(1/2): 1-7. DOI:10.1016/j.etp.2009.09.001
Qin H D Huang D Weng X D Upregulation of peroxisome proliferator-activated receptor-gamma and NADPH oxidases are involved in restenosis after balloon injury J Cell Physiol 2009 221 2 387 393 10.1002/jcp.21865 Qin H D, Huang D, Weng X D, et al . Upregulation of peroxisome proliferator-activated receptor-gamma and NADPH oxidases are involved in restenosis after balloon injury[J ] . J Cell Physiol, 2009, 221(2): 387-393.DOI: 10.1002/jcp.21865
Gizard F Bruemmer D Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-gamma: Therapeutic Implications for Cardiovascular Diseases PPAR Res 2008 2008 429123 10.1155/2008/429123 Gizard F, Bruemmer D. Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-gamma: Therapeutic Implications for Cardiovascular Diseases[J]. PPAR Res, 2008, 2008: 429123.DOI: 10.1155/2008/429123
杨 源瑞 郑 波 周 振华 猪颈动脉支架植入术后PPAR- γ 的表达变化及对血管平滑肌表型转化的影响 第三军医大学学报 2014 36 4 321 325 http://aammt.tmmu.edu.cn/oa/DArticle.aspx?type=view&id=201309139 杨源瑞, 郑波, 周振华, 等.猪颈动脉支架植入术后PPAR- γ 的表达变化及对血管平滑肌表型转化的影响[J ] .第三军医大学学报, 2014, 36(4): 321-325. DOI:10.16016/j.1000-5404.2014.04.011
Kim J S Kim I K Lee S Y Anti-proliferative effect of rosiglitazone on angiotensin Ⅱ-induced vascular smooth muscle cell proliferation is mediated by the mTOR pathway Cell Biol Int 2012 36 3 305 310 10.1042/CBI20100524 Kim J S, Kim I K, Lee S Y, et al . Anti-proliferative effect of rosiglitazone on angiotensin Ⅱ-induced vascular smooth muscle cell proliferation is mediated by the mTOR pathway[J ] . Cell Biol Int, 2012, 36(3): 305-310.DOI: 10.1042/CBI20100524
Ji Y Liu J Wang Z PPARgamma agonist, rosiglitazone, regulates angiotensin Ⅱ-induced vascular inflammation through the TLR4-dependent signaling pathway Lab Invest 2009 89 8 887 902 10.1038/labinvest.2009.45 Ji Y, Liu J, Wang Z, et al . PPARgamma ag onist, rosiglitazone, regulates angiotensin Ⅱ-induced vascular inflammation through the TLR4-dependent signaling pathway[J ] .Lab Invest, 2009, 89(8): 887-902. DOI:10.1038/labinvest.2009.45
Chen H F Xie L D Xu C S The signal transduction pathways of heat shock protein 27 phosphorylation in vascular smooth muscle cells Mol Cell Biochem 2010 333 1/2 49 56 10.1007/s11010-009-0203-5 Chen H F, Xie L D, Xu C S. The signal transduction pathways of heat shock protein 27 phosphorylation in vascular smooth muscle cells[J]. Mol Cell Biochem, 2010, 333(1/2): 49-56.DOI: 10.1007/s11010-009-0203-5
Ayari H Legedz L Cerutti C Mutual amplification of corticosteroids and angiotensin systems in human vascular smooth muscle cells and carotid atheroma J Mol Med (Berl) 2014 92 11 1201 1208 10.1007/s00109-014-1193-7 Ayari H, Legedz L, Cerutti C, et al . Mutual amplification of corticosteroids and angiotens in systems in human vascular smooth muscle cells and carotid atheroma[J ] . J Mol Med (Berl), 2014, 92(11):1201-1208.DOI:10.1007/s00109-014-1193-7
Sabri A Levy B I Poitevin P Differential roles of AT1 and AT2 receptor subtypes in vascular trophic and phenotypic changes in response to stimulation with angiotensin Ⅱ Arterioscler Thromb Vasc Biol 1997 17 2 257 264 10.1161/01.ATV.17.2.257 Sabri A, Levy B I, Poitevin P, et al . Differential roles of AT1 and AT2 receptor subtypes in vascular trophic and phenotypic changes in response to stimulation with angiotensin Ⅱ[J ] . Arterioscler Thromb Vasc Biol, 1997, 17(2): 257-264.
Yi B Cui J Ning J N Over-expression of PKGIalpha inhibits hypoxia-induced proliferation, Akt activation, and phenotype modulation of human PASMCs: the role of phenotype modulation of PASMCs in pulmonary vascular remodeling Gene 2012 492 2 354 360 10.1016/j.gene.2011.11.010 Yi B, Cui J, Ning J N, et al . Over-expression of PKGIalpha inhibits hypoxia-induced proliferation, Akt activation, and phenotype modulation of human PASMCs: the role of phenotype modulation of PASMCs in pulmonary vascular remodeling[J ] .Gene, 2012, 492(2):354-360.DOI:10.1016/j.gene.2011.11.010
Sugawara A Takeuchi K Uruno A Transcriptional suppression of type 1 angiotensin Ⅱ receptor gene expression by peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells Endocrinology 2001 142 7 3125 3134 10.1210/endo.142.7.8272 Sugawara A, Takeuchi K, Uruno A, et al . Transcriptional suppression of type 1 angiotensin Ⅱ receptor gene expression by peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells[J ] . Endocrinology, 2001, 142(7): 3125-3134.DOI: 10.1210/endo.142.7.8272
Takeda K Ichiki T Tokunou T Peroxisome proliferator-activated receptor gamma activators downregulate angiotensin Ⅱ type 1 receptor in vascular smooth muscle cells Circulation 2000 102 15 1834 1839 10.1161/01.CIR.102.15.1834 Takeda K, Ichiki T, Tokunou T, et al . Peroxisome proliferator-activated receptor gamma activators downregulate angiotensin Ⅱ type 1 receptor in vascular smooth muscle cells[J ] . Circulation, 2000, 102(15): 1834-1839.
Gao D F Niu X L Hao G H Rosiglitazone inhibits angiotensin Ⅱ-induced CTGF expression in vascular smooth muscle cells-role of PPAR-gamma in vascular fibrosis Biochem Pharmacol 2007 73 2 185 197 10.1016/j.bcp.2006.09.019 Gao D F, Niu X L, Hao G H, et al . Rosiglitazone inhibits angiotensin Ⅱ-induced CTGF expression in vascular smooth muscle cells-role of PPAR-gamma in vascular fibrosis[J ] . Biochem Pharmacol, 2007, 73(2): 185-197. DOI:10.1016/j.bcp.2006.09.019
Sugawara A Takeuchi K Uruno A Differential effects among thiazolidinediones on the transcription of thromboxane receptor and angiotensin Ⅱ type 1 receptor genes Hypertens Res 2001 24 3 229 233 10.1291/hypres.24.229 Sugawara A, Takeuchi K, Uruno A, et al . Differential effects among thiazolidinediones on the transcription of thromboxane receptor and angiotensin Ⅱ type 1 receptor genes[J ] . Hypertens Res, 2001, 24(3): 229-233.
Yi B Cui J Ning J N Over-expression of PKGIalpha inhibits hypoxia-induced proliferation, Akt activation, and phenotype modulation of human PASMCs: the role of phenotype modulation of PASMCs in pulmonary vascular remodeling Gene 2012 492 2 354 360 10.1016/j.gene.2011.11.010 Yi B, Cui J, Ning J N, et al . Over-expression of PKGIalpha inhibits hypoxia-induced proliferation, Akt activation, and phenotype modulation of human PASMCs: the role of phenotype modulation of PASMCs in pulmonary vascular remodeling[J ] . Gene, 2012, 492(2): 354-360. DOI:10.1016/j.gene.2011.11.010
Yang H M Kim B K Kim J Y PPAR γ modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury Exp Mol Med 2013 45 11 e65 10.1038/emm.2013.112 Yang H M, Kim B K, Kim J Y, et al . PPAR γ modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury[J ] . Exp Mol Med, 2013, 45(11): e65.DOI: 10.1038/emm.2013.112
Krentz A Thiazolidinediones: effects on the development and progression of type 2 diabetes and associated vascular complications Diabetes Metab Res Rev 2009 25 2 112 126 10.1002/dmrr.937 Krentz A. Thiazolidinediones: effects on the development and progression of type 2 diabetes and associated vascular complications[J]. Diabetes Metab Res Rev, 2009, 25(2): 112-126.DOI: 10.1002/dmrr.937
Home P D Pocock S J Beck-Nielsen H Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial Lancet 2009 373 9681 2125 2135 10.1016/S0140-6736(09)60953-3 Home P D, Pocock S J, Beck-Nielsen H, et al . Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial[J ] . Lancet, 2009, 373(9681):2125-2135.DOI:10.1016/S0140-6736(09)60953-3
0
Views
0
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621
