Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Artemisinin attenuates platelet-derived growth factor BB-induced migration of vascular smooth muscle cells

  • Lee, Kang Pa (Department of Medical Science, School of Medicine Konkuk University) ;
  • Park, Eun-Seok (Department of Biomedical Laboratory Science, Kyungbok University) ;
  • Kim, Dae-Eun (Department of Biomedical Laboratory Science, Kyungbok University) ;
  • Park, In-Sik (Department of Anatomy, College of Korean Medicine, Dongguk University) ;
  • Kim, Jin Tack (Department of Anatomy, College of Korean Medicine, Dongguk University) ;
  • Hong, Heeok (Department of Medical Science, School of Medicine Konkuk University)
  • Received : 2014.04.22
  • Accepted : 2014.07.25
  • Published : 2014.10.01
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Abstract

BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effect of AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferation of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migration was measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by using an EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measured through $H_2DCF$-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measures of extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9 measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT ($10{\mu}M$ and $30{\mu}M$) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependent manner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BB stimulated VSMC treated with AT ($10{\mu}M$ and $30{\mu}M$) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expression compared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulated VSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.

Keywords

References

  1. Ministry of Health and Welfare, Korea Centers for Disease Control and Prevention. Korea Health Statistics 2012: Korea National Health and Nutrition Examination Survey (KNHANES V-3). Cheongwon: Korea Centers for Disease Control and Prevention; 2013.
  2. Buttari B, Profumo E, Businaro R, Saso L, Capoano R, Salvati B, Rigano R. Oxidized haemoglobin-driven endothelial dysfunction and immune cell activation: novel therapeutic targets for atherosclerosis. Curr Med Chem 2013;20:4806-14. https://doi.org/10.2174/09298673113209990162
  3. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801-9. https://doi.org/10.1038/362801a0
  4. Shah PK. Inflammation, neointimal hyperplasia, and restenosis: as the leukocytes roll, the arteries thicken. Circulation 2003;107:2175-7. https://doi.org/10.1161/01.CIR.0000069943.41206.BD
  5. Kondo T, Konishi F, Inui H, Inagami T. Differing signal transductions elicited by three isoforms of platelet-derived growth factor in vascular smooth muscle cells. J Biol Chem 1993;268:4458-64.
  6. Ross R, Raines EW, Bowen-Pope DF. The biology of platelet-derived growth factor. Cell 1986;46:155-69. https://doi.org/10.1016/0092-8674(86)90733-6
  7. Park SS, Kim WJ, Moon SK. Role of decursin in TNF-${\alpha}$-stimulated migration, invasion, and matrix metalloproteinase-9 induction in vascular smooth muscle cells. Food Sci Biotechnol 2011;20:913-8. https://doi.org/10.1007/s10068-011-0126-2
  8. Moon CY, Ku CR, Cho YH, Lee EJ. Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth muscle cells and intravascular thrombosis. Biochem Biophys Res Commun 2012;423: 116-21. https://doi.org/10.1016/j.bbrc.2012.05.092
  9. Lyle AN, Griendling KK. Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda) 2006; 21:269-80. https://doi.org/10.1152/physiol.00004.2006
  10. Kyaw M, Yoshizumi M, Tsuchiya K, Kirima K, Tamaki T. Antioxidants inhibit JNK and p38 MAPK activation but not ERK 1/2 activation by angiotensin II in rat aortic smooth muscle cells. Hypertens Res 2001;24:251-61. https://doi.org/10.1291/hypres.24.251
  11. Zhou Y, Yan H, Guo M, Zhu J, Xiao Q, Zhang L. Reactive oxygen species in vascular formation and development. Oxid Med Cell Longev 2013;2013:374963.
  12. Park J, Ha H, Seo J, Kim MS, Kim HJ, Huh KH, Park K, Kim YS. Mycophenolic acid inhibits platelet-derived growth factor-induced reactive oxygen species and mitogen-activated protein kinase activation in rat vascular smooth muscle cells. Am J Transplant 2004;4:1982-90. https://doi.org/10.1111/j.1600-6143.2004.00610.x
  13. Bornfeldt KE, Raines EW, Nakano T, Graves LM, Krebs EG, Ross R. Insulin-like growth factor-I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation. J Clin Invest 1994;93:1266-74. https://doi.org/10.1172/JCI117081
  14. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003;92:827-39. https://doi.org/10.1161/01.RES.0000070112.80711.3D
  15. Kohler M, Haerdi W, Christen P, Veuthey JL. Extraction of artemisinin and artemisinic acid from Artemisia annua L. using supercritical carbon dioxide. J Chromatogr A 1997;785:353-60. https://doi.org/10.1016/S0021-9673(97)00403-2
  16. Ho WE, Peh HY, Chan TK, Wong WS. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther 2014;142:126-39. https://doi.org/10.1016/j.pharmthera.2013.12.001
  17. Won KJ, Lee SC, Lee CK, Lee HM, Lee SH, Fang Z, Choi OB, Jin M, Kim J, Park T, Choi WS, Kim SK, Kim B. Cordycepin attenuates neointimal formation by inhibiting reactive oxygen species-mediated responses in vascular smooth muscle cells in rats. J Pharmacol Sci 2009;109:403-12. https://doi.org/10.1254/jphs.08308FP
  18. Singh NP, Lai HC. Artemisinin induces apoptosis in human cancer cells. Anticancer Res 2004;24:2277-80.
  19. Choi OB, Park JH, Lee YJ, Lee CK, Won KJ, Kim J, Lee HM, Kim B. Olibanum extract inhibits vascular smooth muscle cell migration and proliferation in response to platelet-derived growth factor. Korean J Physiol Pharmacol 2009;13:107-13. https://doi.org/10.4196/kjpp.2009.13.2.107
  20. Jiang D, Li D, Wu W. Inhibitory effects and mechanisms of luteolin on proliferation and migration of vascular smooth muscle cells. Nutrients 2013;5:1648-59. https://doi.org/10.3390/nu5051648
  21. Konneh MK, Rutherford C, Li SR, Anggard EE, Ferns GA. Vitamin E inhibits the intimal response to balloon catheter injury in the carotid artery of the cholesterol-fed rat. Atherosclerosis 1995;113: 29-39. https://doi.org/10.1016/0021-9150(94)05423-G

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