Abstract
Vascular smooth muscle cell proliferation is a key event in the development of hypertension, instant restenosis and other cardiac disorders. Inhibition of this proliferation could lead to better prevention and treatment of these diseases. This study was designed to investigate the effects and mechanisms of different concentrations of xanthinol nicotinate (XN) on human umbilical artery smooth muscle cell (HUASMC) proliferation in vitro. HUASMCs were cultured by the tissue adherent method, passaged three times, and then identified by immunohistochemistry. HUASMCs were then treated with different concentrations of XN (0, 2.76, 27.6 or 276 µM), and a 3-(4,5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to detect the inhibition of HUASMC proliferation. The levels of platelet-derived growth factor receptor (PDGFR) mRNA and protein (PDGFR-β) were detected on the cell membrane of these treated HUASMCs using RT-PCR and Western blot analysis, respectively. After culturing and passaging three times, 90 % of the cultured cells were identified as HUASMCs by immunohistochemistry. HUASMC proliferation was inhibited by XN in a dose-dependent manner (P < 0.05). Furthermore, XN dose-dependently decreased the PDGFR mRNA and PDGFR-β levels on the cell membranes of HUASMCs (P < 0.05). Thus, the results suggest that XN could become a potent therapeutic agent for regulating VSMC-associated vascular disease such as cardiovascular disease and restenosis after angioplasty.





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Bell L, Madri JA (1990) Influence of the angiotensin system on endothelial and smooth muscle cell migration. Am J Pathol 137(1):7–12
Bornfeldt KE, Raines EW, Nakano T, Graves LM, Krebs EG, Ross R (1994) 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 93(3):1266–1274
Callow AD (2006) Cardiovascular disease 2005—the global picture. Vascul Pharmacol 45(5):302–307
Cardus A, Parisi E, Gallego C, Aldea M, Fernandez E, Valdivielso JM (2006) 1,25-Dihydroxyvitamin D3 stimulates vascular smooth muscle cell proliferation through a VEGF-mediated pathway. Kidney Int 69(8):1377–1384
Chen PY, Simons M, Friesel R (2009) FRS2 via fibroblast growth factor receptor 1 is required for platelet-derived growth factor receptor beta-mediated regulation of vascular smooth muscle marker gene expression. J Biol Chem 284(23):15980–15992
Fredriksson L, Li H, Eriksson U (2004) The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev 15(4):197–204
Galal E, Moustafa M, El-Gohary N, El-Mahdy SA, El-S AH, Radwan AG (1976) Pharmacological evaluation of xanthinol nicotinate (complamin). J Egypt Med Assoc 59(1–2):141–149
Goetze S, Xi XP, Kawano H et al (1999) PPAR gamma-ligands inhibit migration mediated by multiple chemoattractants in vascular smooth muscle cells. J Cardiovasc Pharmacol 33(5):798–806
Granata R, Settanni F, Gallo D et al (2008) Obestatin promotes survival of pancreatic beta-cells and human islets and induces expression of genes involved in the regulation of beta-cell mass and function. Diabetes 57(4):967–979
Greenberg JI, Shields DJ, Barillas SG et al (2008) A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 456(7223):809–813
Grotendorst GR, Seppa HE, Kleinman HK, Martin GR (1981) Attachment of smooth muscle cells to collagen and their migration toward platelet-derived growth factor. Proc Natl Acad Sci USA 78(6):3669–3672
Higashiyama S, Abraham JA, Klagsbrun M (1993) Heparin-binding EGF-like growth factor stimulation of smooth muscle cell migration: dependence on interactions with cell surface heparan sulfate. J Cell Biol 122(4):933–940
Hossain MZ, Ao P, Boynton AL (1998) Rapid disruption of gap junctional communication and phosphorylation of connexin43 by platelet-derived growth factor in T51B rat liver epithelial cells expressing platelet-derived growth factor receptor. J Cell Physiol 174(1):66–77
Hu SS, Kong LZ, Gao RL et al (2012) Outline of the report on cardiovascular disease in China, 2010. Biomed Environ Sci 25(3):251–256
Inta I, Weber D, Grundt C et al (2009) Correlation of soluble gp130 serum concentrations with arterial blood pressure. J Hypertens 27(3):527–534
Ishida A, Murray J, Saito Y et al (2001) Expression of vascular endothelial growth factor receptors in smooth muscle cells. J Cell Physiol 188(3):359–368
Jackson CL, Raines EW, Ross R, Reidy MA (1993) Role of endogenous platelet-derived growth factor in arterial smooth muscle cell migration after balloon catheter injury. Arterioscler Thromb 13(8):1218–1226
Jandt E, Mutschke O, Mahboobi S et al (2010) Stent-based release of a selective PDGF-receptor blocker from the bis-indolylmethanon class inhibits restenosis in the rabbit animal model. Vascul Pharmacol 52(1–2):55–62
Kanwar SS, Yu Y, Nautiyal J, Patel BB, Majumdar AP (2010) The Wnt/beta-catenin pathway regulates growth and maintenance of colonospheres. Mol Cancer 9:212
Kim SY, Jeoung NH, Oh CJ et al (2009) Activation of NAD(P)H:quinone oxidoreductase 1 prevents arterial restenosis by suppressing vascular smooth muscle cell proliferation. Circ Res 104(7):842–850
Kim SY, Ryu SJ, Ahn HJ, Choi HR, Kang HT, Park SC (2010) Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression. Biochem Biophys Res Commun 391(1):28–32
Liang CJ, Ives HE, Yang CM, Ma YH (2008) 20-HETE inhibits the proliferation of vascular smooth muscle cells via transforming growth factor-beta. J Lipid Res 49(1):66–73
Little PJ, Ivey ME, Osman N (2008) Endothelin-1 actions on vascular smooth muscle cell functions as a target for the prevention of atherosclerosis. Curr Vasc Pharmacol 6(3):195–203
Merwin JR, Newman W, Beall LD, Tucker A, Madri J (1991) Vascular cells respond differentially to transforming growth factors beta 1 and beta 2 in vitro. Am J Pathol 138(1):37–51
Noda-Heiny H, Sobel BE (1995) Vascular smooth muscle cell migration mediated by thrombin and urokinase receptor. Am J Physiol 268(5 Pt 1):C1195–C1201
Nomoto A, Mutoh S, Hagihara H, Yamaguchi I (1988) Smooth muscle cell migration induced by inflammatory cell products and its inhibition by a potent calcium antagonist, nilvadipine. Atherosclerosis 72(2–3):213–219
Segers J, Crokart N, Danhier P, Gregoire V, Jordan BF, Gallez B (2010) Use of xanthinol nicotinate as a co-treatment for radio- and chemo-therapy in experimental tumors. Int J Cancer 126(2):583–588
Shyu KG, Wang BW, Chang H (2009) Hyperbaric oxygen activates discoidin domain receptor 2 via tumour necrosis factor-alpha and the p38 MAPK pathway to increase vascular smooth muscle cell migration through matrix metalloproteinase 2. Clin Sci (Lond) 116(7):575–583
Stepanova V, Bobik A, Bibilashvily R et al (1997) Urokinase plasminogen activator induces smooth muscle cell migration: key role of growth factor-like domain. FEBS Lett 414(2):471–474
Urata Y, Goto S, Kawakatsu M et al (2010) DHEA attenuates PDGF-induced phenotypic proliferation of vascular smooth muscle A7r5 cells through redox regulation. Biochem Biophys Res Commun 396(2):489–494
Vadiveloo PK, Stanton HR, Cochran FW, Hamilton JA (1994) Interleukin-4 inhibits human smooth muscle cell proliferation. Artery 21(3):161–181
Wang Z, Newman WH (2003) Smooth muscle cell migration stimulated by interleukin 6 is associated with cytoskeletal reorganization. J Surg Res 111(2):261–266
Watanabe S, Mu W, Kahn A et al (2004) Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle cells. Am J Nephrol 24(4):387–392
Wosniak JJ, Santos CX, Kowaltowski AJ, Laurindo FR (2009) Cross-talk between mitochondria and NADPH oxidase: effects of mild mitochondrial dysfunction on angiotensin II-mediated increase in Nox isoform expression and activity in vascular smooth muscle cells. Antioxid Redox Signal 11(6):1265–1278
Yang JY, Wang Q, Wang W, Zeng LF (2015) Histone deacetylases and cardiovascular cell lineage commitment. World J Stem Cells 7(5):852–858
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This work was financially supported by the Postdoctoral Research Foundation of Heilongjiang Province, China (Grant No. LRB05-230).
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Xiaodan Bai and Lijun Huang have contributed equally to this work.
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Bai, X., Huang, L., Hu, K. et al. Inhibited proliferation of human umbilical artery smooth muscle cells by xanthinol nicotinate. Med Biol Eng Comput 54, 891–898 (2016). https://doi.org/10.1007/s11517-015-1438-9
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DOI: https://doi.org/10.1007/s11517-015-1438-9