Resveratrol Inhibits Restenosis through Suppressing Proliferation, Migration and Trans-differentiation of Vascular Adventitia Fibroblasts via Activating SIRT1


Cite item

Full Text

Abstract

Aim:After the balloon angioplasty, vascular adventitia fibroblasts (VAFs), which proliferate, trans-differentiate to myofibroblasts and migrate to neointima, are crucial in restenosis. Resveratrol (RSV) has been reported to protect the cardiovascular by reducing restenosis and the mechanism remains unclear.

Methods:This study was dedicated to investigate the effect of RSV on VAFs in injured arteries and explore the potential mechanism. In this work, carotid artery balloon angioplasty was performed on male SD rats to ensure the injury of intima and VAFs were isolated to explore the effects in vitro. The functional and morphological results showed the peripheral delivery of RSV decreased restenosis of the injured arteries and suppressed the expression of proliferation, migration and transformation related genes. Moreover, after being treated with RSV, the proliferation, migration and trans-differentiation of VAFs were significantly suppressed and exogenous TGF-β1 can reverse this effect.

Result:Mechanistically, RSV administration activated SIRT1 and decreased the translation and expression of TGF-β1, SMAD3 and NOX4, and reactive oxygen species (ROS) decreased significantly after VAFs treated with RSV.

Conclusion:Above results indicated RSV inhibited restenosis after balloon angioplasty through suppressing proliferation, migration and trans-differentiation of VAFs via regulating SIRT1- TGF-β1-SMAD3-NOX4 to decrease ROS.

About the authors

Mengyun Li

Department of Anesthesiology, Zhongnan Hospital of Wuhan University

Email: info@benthamscience.net

Lan Luo

Department of Anesthesiology, First People's Hospital of Foshan

Email: info@benthamscience.net

Ying Xiong

Department of Anesthesiology, Zhongnan Hospital of Wuhan University

Email: info@benthamscience.net

Fuyu Wang

Department of Anesthesiology, Zhongnan Hospital of Wuhan University

Email: info@benthamscience.net

Yun Xia

Department of Anesthesiology, Zhongnan Hospital of Wuhan University

Email: info@benthamscience.net

Zongze Zhang

Department of Anesthesiology, Zhongnan Hospital of Wuhan University

Author for correspondence.
Email: info@benthamscience.net

Jianjuan Ke

Department of Anesthesiology, Zhongnan Hospital of Wuhan University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Wu, Y.; Liu, X.; Guo, L.Y.; Zhang, L.; Zheng, F.; Li, S.; Li, X.Y.; Yuan, Y.; Liu, Y.; Yan, Y.; Chen, S.Y.; Wang, J.N.; Zhang, J.; Tang, J.M. S100B is required for maintaining an intermediate state with double-positive Sca-1+ progenitor and vascular smooth muscle cells during neointimal formation. Stem Cell Res. Ther., 2019, 10(1), 294. doi: 10.1186/s13287-019-1400-0 PMID: 31547879
  2. Mota, R.I.; Morgan, S.E.; Bahnson, E.M. Diabetic vasculopathy: Macro and microvascular injury. Curr. Pathobiol. Rep., 2020, 8(1), 1-14. doi: 10.1007/s40139-020-00205-x PMID: 32655983
  3. Simard, T.; Hibbert, B.; Ramirez, F.D.; Froeschl, M.; Chen, Y.X.; O’Brien, E.R. The evolution of coronary stents: A brief review. Can. J. Cardiol., 2014, 30(1), 35-45. doi: 10.1016/j.cjca.2013.09.012 PMID: 24286961
  4. Marquis-Gravel, G.; Matteau, A.; Potter, B.J.; Gobeil, F.; Noiseux, N.; Stevens, L.M.; Mansour, S. Impact of paclitaxel-eluting balloons compared to second-generation drug-eluting stents for of in-stent restenosis in a primarily acute coronary syndrome population. Arq. Bras. Cardiol., 2017, 109(4), 277-283. doi: 10.5935/abc.20170142 PMID: 28977052
  5. Jeewandara, T.; Wise, S.; Ng, M. Biocompatibility of coronary stents. Materials (Basel), 2014, 7(2), 769-786. doi: 10.3390/ma7020769 PMID: 28788487
  6. Peng, X.; Qu, W.; Jia, Y.; Wang, Y.; Yu, B.; Tian, J. Bioresorbable scaffolds: Contemporary status and future directions. Front. Cardiovasc. Med., 2020, 7, 589571. doi: 10.3389/fcvm.2020.589571 PMID: 33330651
  7. Yang, X.; Yang, Y.; Guo, J.; Meng, Y.; Li, M.; Yang, P.; Liu, X.; Aung, L.H.H.; Yu, T.; Li, Y. Targeting the epigenome in in-stent restenosis: From mechanisms to therapy. Mol. Ther. Nucleic Acids, 2021, 23, 1136-1160. doi: 10.1016/j.omtn.2021.01.024 PMID: 33664994
  8. Guo, L.W.; Wang, B.; Goel, S.A.; Little, C.; Takayama, T.; Shi, X.D.; Roenneburg, D.; DiRenzo, D.; Kent, K.C. Halofuginone stimulates adaptive remodeling and preserves re-endothelialization in balloon-injured rat carotid arteries. Circ. Cardiovasc. Interv., 2014, 7(4), 594-601. doi: 10.1161/CIRCINTERVENTIONS.113.001181 PMID: 25074254
  9. Xie, X.; Urabe, G.; Marcho, L.; Stratton, M.; Guo, L.W.; Kent, C.K. ALDH1A3 regulations of matricellular proteins promote vascular smooth muscle cell proliferation. iScience, 2019, 19, 872-882. doi: 10.1016/j.isci.2019.08.044 PMID: 31513972
  10. Satish, L.; LaFramboise, W.A.; O’Gorman, D.B.; Johnson, S.; Janto, B.; Gan, B.S.; Baratz, M.E.; Hu, F.Z.; Post, J.C.; Ehrlich, G.D.; Kathju, S. Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren’s Contracture. BMC Med. Genomics, 2008, 1(1), 10. doi: 10.1186/1755-8794-1-10 PMID: 18433489
  11. Sasaki, N.; Toyoda, M. Vascular diseases and gangliosides. Int. J. Mol. Sci., 2019, 20(24), 6362. doi: 10.3390/ijms20246362 PMID: 31861196
  12. Han, X.; Wu, A.; Wang, J.; Chang, H.; Zhao, Y.; Zhang, Y.; Mao, Y.; Lou, L.; Gao, Y.; Zhang, D.; Li, T.; Yang, T.; Wang, L.; Feng, C.; Zhao, M. Activation and migration of adventitial fibroblasts contributes to vascular remodeling Anat. Rec., 2018, 301, 1216-1223.
  13. Wu, X.; Lu, Q. Expression and significance of α-SMA and PCNA in the vascular adventitia of balloon-injured rat aorta. Exp. Ther. Med., 2013, 5(6), 1671-1676. doi: 10.3892/etm.2013.1059 PMID: 23837052
  14. Yan, C.; Li, B.; Fan, F.; Du, Y.; Ma, R.; Cheng, X.D.; Li, X.Y.; Zhang, B.; Yu, Q.; Wang, Y.G.; Tang, R.X.; Zheng, K.Y. The roles of Toll-like receptor 4 in the pathogenesis of pathogen-associated biliary fibrosis caused by Clonorchis sinensis. Sci. Rep., 2017, 7(1), 3909. doi: 10.1038/s41598-017-04018-8 PMID: 28634394
  15. Ren, M.; Zhang, J.; Wang, B.; Liu, P.; Jiang, H.; Liu, G.; Yin, H. Qindan-capsule inhibits proliferation of adventitial fibroblasts and collagen synthesis. J. Ethnopharmacol., 2010, 129(1), 53-58. doi: 10.1016/j.jep.2010.03.004 PMID: 20230887
  16. Chen, W.; Chu, Y.; Zhu, D.; Yan, C.; Liu, J.; Ji, K.; Gao, P. Perivascular gene transfer of dominant-negative N19RhoA attenuates neointimal formation via inhibition of TGF-β1-Smad2 signaling in rats after carotid artery balloon injury. Biochem. Biophys. Res. Commun., 2009, 389(2), 217-223. doi: 10.1016/j.bbrc.2009.08.104 PMID: 19706289
  17. Wang, M.; Xiong, L.; Jiang, L.J.; Lu, Y.Z.; Liu, F.; Song, L.J.; Xiang, F.; He, X.L.; Yu, F.; Shuai, S.Y.; Ma, W.L.; Ye, H. miR-4739 mediates pleural fibrosis by targeting bone morphogenetic protein 7. EBioMedicine, 2019, 41, 670-682. doi: 10.1016/j.ebiom.2019.02.057 PMID: 30850350
  18. Zhang, H.; Wang, Y.; Meng, A.; Yan, H.; Wang, X.; Niu, J.; Li, J.; Wang, H. Inhibiting TGFβ1 has a protective effect on mouse bone marrow suppression following ionizing radiation exposure in vitro. J. Radiat. Res., 2013, 54(4), 630-636. doi: 10.1093/jrr/rrs142 PMID: 23370919
  19. Zhu, Y.; Takayama, T.; Wang, B.; Kent, A.; Zhang, M.; Binder, B.Y.K.; Urabe, G.; Shi, Y.; DiRenzo, D.; Goel, S.A.; Zhou, Y.; Little, C.; Roenneburg, D.A.; Shi, X.D.; Li, L.; Murphy, W.L.; Kent, K.C.; Ke, J.; Guo, L.W. Restenosis inhibition and re-differentiation of TGFβ/smad3-activated smooth muscle cells by resveratrol. Sci. Rep., 2017, 7(1), 41916. doi: 10.1038/srep41916 PMID: 28165488
  20. Barman, S.A.; Fulton, D. Adventitial fibroblast Nox4 expression and ROS signaling in pulmonary arterial hypertension. Adv. Exp. Med. Biol., 2017, 967, 1-11. doi: 10.1007/978-3-319-63245-2_1 PMID: 29047077
  21. Li, S.; Tabar, S.S.; Malec, V.; Eul, B.G.; Klepetko, W.; Weissmann, N.; Grimminger, F.; Seeger, W.; Rose, F.; Hänze, J. NOX4 regulates ROS levels under normoxic and hypoxic conditions, triggers proliferation, and inhibits apoptosis in pulmonary artery adventitial fibroblasts. Antioxid. Redox Signal., 2008, 10(10), 1687-1698. doi: 10.1089/ars.2008.2035 PMID: 18593227
  22. Zhang, S.; Yin, Z.; Qin, W.; Ma, X.; Zhang, Y.; Liu, E.; Chu, Y. Pirfenidone inhibits hypoxic pulmonary hypertension through the NADPH/ROS/p38 pathway in adventitial fibroblasts in the pulmonary artery. Mediators Inflamm., 2020, 2020, 1-12. doi: 10.1155/2020/2604967 PMID: 32587469
  23. Barnes, J.L.; Gorin, Y. Myofibroblast differentiation during fibrosis: Role of NAD(P)H oxidases. Kidney Int., 2011, 79(9), 944-956. doi: 10.1038/ki.2010.516 PMID: 21307839
  24. Xu, F.; Liu, Y.; Shi, L.; Liu, W.; Zhang, L.; Cai, H.; Qi, J.; Cui, Y.; Wang, W.; Hu, Y. NADPH oxidase p47phox siRNA attenuates adventitial fibroblasts proliferation and migration in apoE(-/-) mouse. J. Transl. Med., 2015, 13(1), 38. doi: 10.1186/s12967-015-0407-2 PMID: 25628043
  25. Janbandhu, V.; Tallapragada, V.; Patrick, R.; Li, Y.; Abeygunawardena, D.; Humphreys, D.T.; Martin, E.M.M.A.; Ward, A.O.; Contreras, O.; Farbehi, N.; Yao, E.; Du, J.; Dunwoodie, S.L.; Bursac, N.; Harvey, R.P. Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction. Cell Stem Cell, 2022, 29(2), 281-297.e12. doi: 10.1016/j.stem.2021.10.009 PMID: 34762860
  26. Vallée, A.; Lecarpentier, Y.; Vallée, J.N. Thermodynamic aspects and reprogramming cellular energy metabolism during the fibrosis process. Int. J. Mol. Sci., 2017, 18(12), 2537. doi: 10.3390/ijms18122537 PMID: 29186898
  27. Chatterjee, A.; Kosmacek, E.A.; Oberley-Deegan, R.E. MnTE-2-PyP treatment, or NOX4 inhibition, protects against radiation-induced damage in mouse primary prostate fibroblasts by inhibiting the TGF-Beta 1 signaling pathway. Radiat. Res., 2017, 187(3), 367-381. doi: 10.1667/RR14623.1 PMID: 28225655
  28. Morry, J.; Ngamcherdtrakul, W.; Yantasee, W. Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles. Redox Biol., 2017, 11, 240-253. doi: 10.1016/j.redox.2016.12.011 PMID: 28012439
  29. Benedetti, F.; Sorrenti, V.; Buriani, A.; Fortinguerra, S.; Scapagnini, G.; Zella, D. Resveratrol, rapamycin and metformin as modulators of antiviral pathways. Viruses, 2020, 12(12), 1458. doi: 10.3390/v12121458 PMID: 33348714
  30. Gharaee-Kermani, M.; Moore, B.B.; Macoska, J.A. Resveratrol-mediated repression and reversion of prostatic myofibroblast phenoconversion. PLoS One, 2016, 11(7), e0158357. doi: 10.1371/journal.pone.0158357 PMID: 27367854
  31. Malaguarnera, L. Influence of resveratrol on the immune response. Nutrients, 2019, 11(5), 946. doi: 10.3390/nu11050946 PMID: 31035454
  32. Zerr, P.; Palumbo-Zerr, K.; Huang, J.; Tomcik, M.; Sumova, B.; Distler, O.; Schett, G.; Distler, J.H.W. Sirt1 regulates canonical TGF-β signalling to control fibroblast activation and tissue fibrosis. Ann. Rheum. Dis., 2016, 75(1), 226-233. doi: 10.1136/annrheumdis-2014-205740 PMID: 25180292
  33. Si, J.; Meng, R.; Gao, P.; Hui, F.; Li, Y.; Liu, X.; Yang, B. Linagliptin protects rat carotid artery from balloon injury and activates the NRF2 antioxidant pathway. Exp. Anim., 2019, 68(1), 81-90. doi: 10.1538/expanim.18-0089 PMID: 30369549
  34. Wang, X.W.; Zhang, C.; Lee, K.C.; He, X.J.; Lu, Z.Q.; Huang, C.; Wu, Q.C. Adenovirus-mediated gene transfer of microRNA-21 sponge inhibits neointimal hyperplasia in rat vein grafts. Int. J. Biol. Sci., 2017, 13(10), 1309-1319. doi: 10.7150/ijbs.20254 PMID: 29104497
  35. Yu, X.; Takayama, T.; Goel, S.A.; Shi, X.; Zhou, Y.; Kent, K.C.; Murphy, W.L.; Guo, L.W. A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia. J. Control. Release, 2014, 191, 47-53.
  36. Hu, H.; Patel, S.; Hanisch, J.J.; Santana, J.M.; Hashimoto, T.; Bai, H.; Kudze, T.; Foster, T.R.; Guo, J.; Yatsula, B.; Tsui, J.; Dardik, A. Future research directions to improve fistula maturation and reduce access failure. Semin. Vasc. Surg., 2016, 29(4), 153-171. doi: 10.1053/j.semvascsurg.2016.08.005 PMID: 28779782
  37. Liu, L.; Li, N.; Zhang, Q.; Zhou, J.; Lin, L.; He, X. Inhibition of ERK1/2 signaling impairs the promoting effects of TGF-β1 on hepatocellular carcinoma cell invasion and epithelial-mesenchymal transition. Oncol. Res., 2017, 25(9), 1607-1616. doi: 10.3727/096504017X14938093512742 PMID: 28492136
  38. Yang, Y.; Wang, Y.; He, Z.; Liu, Y.; Chen, C.; Wang, Y.; Wang, D.W.; Wang, H. Trimetazidine inhibits renal tubular epithelial cells to mesenchymal transition in diabetic rats via upregulation of sirt1. Front. Pharmacol., 2020, 11, 1136. doi: 10.3389/fphar.2020.01136 PMID: 32848753
  39. Li, K.; Zhai, M.; Jiang, L.; Song, F.; Zhang, B.; Li, J.; Li, H.; Li, B.; Xia, L.; Xu, L.; Cao, Y.; He, M.; Zhu, H.; Zhang, L.; Liang, H.; Jin, Z.; Duan, W.; Wang, S. Tetrahydrocurcumin ameliorates diabetic cardiomyopathy by attenuating high glucose-induced oxidative stress and fibrosis via activating the SIRT1 pathway. Oxid. Med. Cell. Longev., 2019, 2019, 1-15. doi: 10.1155/2019/6746907 PMID: 31210844
  40. Zhao, H.; Wang, Z.; Tang, F.; Zhao, Y.; Feng, D.; Li, Y.; Hu, Y.; Wang, C.; Zhou, J.; Tian, X.; Yao, J. Carnosol-mediated Sirtuin 1 activation inhibits Enhancer of Zeste Homolog 2 to attenuate liver fibrosis. Pharmacol. Res., 2018, 128, 327-337. doi: 10.1016/j.phrs.2017.10.013 PMID: 29106960
  41. Zhang, Z.; Zhao, M.; Wang, G. Hsa_circ_0051079 functions as an oncogene by regulating miR-26a-5p/TGF-β1 in osteosarcoma. Cell Biosci., 2019, 9(1), 94. doi: 10.1186/s13578-019-0355-2 PMID: 31798828
  42. Kubiczkova, L.; Sedlarikova, L.; Hajek, R.; Sevcikova, S. TGF-β – an excellent servant but a bad master. J. Transl. Med., 2012, 10(1), 183. doi: 10.1186/1479-5876-10-183 PMID: 22943793
  43. Yang, K.; Dong, W. SIRT1-related signaling pathways and their association with bronchopulmonary dysplasia. Front. Med. (Lausanne), 2021, 8, 595634. doi: 10.3389/fmed.2021.595634 PMID: 33693011
  44. Huang, S.; You, S.; Qian, J.; Dai, C.; Shen, S.; Wang, J.; Huang, W.; Liang, G.; Wu, G. Myeloid differentiation 2 deficiency attenuates AngII-induced arterial vascular oxidative stress, inflammation, and remodeling. Aging (Albany NY), 2021, 13(3), 4409-4427. doi: 10.18632/aging.202402 PMID: 33495414
  45. Maldonado, E.; Rojas, D.A.; Urbina, F.; Solari, A. The use of antioxidants as potential co-adjuvants to treat chronic chagas disease Antioxidants, 2021, 10(7), 1022.
  46. Yuan, B.; Liu, H.; Dong, X.; Pan, X.; Sun, X.; Sun, J.; Pan, L.L. A novel resveratrol analog upregulates SIRT1 expression and ameliorates neointima formation. Front. Cardiovasc. Med., 2021, 8, 756098. doi: 10.3389/fcvm.2021.756098 PMID: 34796214

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers