Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지

Inhibitory Effect of Uncaria Sinensis on Matrix Metalloproteinase-9 Activity and Human Aortic smooth Muscle Cell migration

  • Kwak, Chang-Geun (Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Choi, Dall-Yeong (Department of Pathology, College of Oriental Medicine, Dongguk University)
  • Published : 2006.12.25
Download PDF
⟨ Previous Next ⟩

Abstract

The migration of vascular smooth muscle cells (VSMC) and the production of matrix metallopreteinases-9 (MMP-9) may play a key role in the development of atherosclerosis. In this study, we have more extensively investigated the inhibitory effect of UR on MMP-9 activity and TNF-${\alpha}$ induced human aortic smooth muscle cells (HASMC) migration. The result from gelatin zymography showed that UR inhibited MMP-9 activity in a dose-dependent manner (IC50 = 55 g/ml). In addition, UR strongly inhibited the migration of HASMC induced by TNF-treatment (IC50 = 125 g/ml), although it has very low cytotoxic effect on HASMC (IC50 > 500 g/ml). These results suggest that UR is a potential anti-atherosclerotic agent through inhibition of MMP-9 activity and VSMC migration.

Keywords

References

  1. Ross, R. The pathogenesis of atherosclerosis: an update. N. Engl. J. Med. 314:488-500, 1986 https://doi.org/10.1056/NEJM198602203140806
  2. Chamley-Campbell, J., Campbell, G.R., Ross, R. The smooth muscle cells in culture. Physiol. Rev. 59:1-61, 1979 https://doi.org/10.1152/physrev.1979.59.1.1
  3. Schwartz, R.S., Holmes, D.R., Topol, E.J. The restenosis paradigm revisited: an alternative proposal for cellular mechanisms. J. Am. Coll. Cardiol. 20:1284-1293, 1992 https://doi.org/10.1016/0735-1097(92)90389-5
  4. Ross, R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801-809, 1993 https://doi.org/10.1038/362801a0
  5. Matrisian, L.M. Metalloproteinases and their inhibitors in matrix remodeling. Trends. Genet. 6:121-125, 1990 https://doi.org/10.1016/0168-9525(90)90126-Q
  6. Sasaguri, Y., Murahashi, N., Sugama, K., Kato, S., Hiraoka, K., Satoh, T., Isomoto, H., Morimatsu, M. Development-related changes in matrix metalloproteinase expression in human aortic smooth muscle cells. Lab. Invest. 71:261-269, 1994
  7. GalisZ, S., Muszynski, M., Sukhova, G.K., Simon-Morrissey, E., Unemori, E.N., Lark, M.W., Amento, E., Libby, P. Cytokinestimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ. Res. 75:181-189, 1994 https://doi.org/10.1161/01.RES.75.1.181
  8. Strauss, B.H., Chisholm, R.J., Keeley, F.W., Gotlieb, A.I., Logan, R.A., Armstrong, P.W. Extracellular matrix remodeling after balloon angioplasty injury in a rabbit model of restenosis. Circ. Res. 75:650-658, 1994 https://doi.org/10.1161/01.RES.75.4.650
  9. Woessner, J.F. Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 5:2145-2154, 1991 https://doi.org/10.1096/fasebj.5.8.1850705
  10. Newby, A.C., Zaltsman, A.B., Molecular mechanisms in intimal hyperplasia. J. Pathol. 190:300-309, 2000 https://doi.org/10.1002/(SICI)1096-9896(200002)190:3<300::AID-PATH596>3.0.CO;2-I
  11. Galis, Z.S., Johnson, C., Godin, D., Magid, R., Shipley, J. M., Senior, R.M., Ivan, E., Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ. Res. 91:852-859, 2002 https://doi.org/10.1161/01.RES.0000041036.86977.14
  12. Moon, S.K., Cha, B.Y., Kim, C.H. ERK1/2 mediates TNF-$\alpha$induced matrix metalloproteinase-9 expression in human vascular smooth muscle cells via the regulation of NF-B and AP-1: involvement of the Ras dependent pathway. J. Cell. Physiol. In press. 2003
  13. Cho, A., Graves, J., Reidy, M.A., Mitogen-activated protein kinases mediate matrix metalloproteinase-9 expression in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 20:2527-2532, 2000 https://doi.org/10.1161/01.ATV.20.12.2527
  14. Moon, S.K., Cho, G.O., Jung, S.Y., Gal, S.W., Kwon, T.K., Lee, Y.C., Madamanchi, N.R., Kim, C.H. Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: role of ERK1/2, cellcycle regulation, and matrix metalloproteinase-9. Biochem. Biophys. Res. Commun. 301:1069-1078, 2003 https://doi.org/10.1016/S0006-291X(03)00091-3
  15. Moon, S.K., Cha, B.Y., Kim, C.H. In vitro cellular aging is associated with enhanced proliferative capacity, G1 cell cycle modulation, and matrix metalloproteinase-9 regulation in mouse aortic smooth muscle cells. Arch. Biochem. Biophys. 418:39-48, 2003 https://doi.org/10.1016/S0003-9861(03)00402-8
  16. Brew, K., Dinakarpandian, D., Nagase, H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim. Biophys. Acta. 1477:267-283, 2000 https://doi.org/10.1016/S0167-4838(99)00279-4
  17. Mandal, M., Mandal, A., Das, S., Chakraborti, T., Sajal, C. Clinical implications of matrix metalloproteinases. Mol. Cell. Biochem. 252:305-329, 2003 https://doi.org/10.1023/A:1025526424637
  18. Zempo, N., Koyama, N., Kenagy, R.D., Lea, H.J., Clowes, A. W. Regulation of vascular smooth muscle cell migration and proliferation in vitro and in injured rat arteries by a synthetic matrix metalloproteinase inhibitor. Arterioscler. Thromb. Vasc. Biol. 16:28-33, 1996 https://doi.org/10.1161/01.ATV.16.1.28
  19. Bendeck, M.P., Irvin, C., Reidy, M.A. Inhibition of matrix metalloproteinase activity inhibits smooth muscle cell migration but not neointimal thickening after arterial injury. Circ. Res. 78:38-43, 1996 https://doi.org/10.1161/01.RES.78.1.38
  20. Kenagy, R.D., Vergel, S., Mattsson, E., Bendeck, M., Reidy, M.A., Clowes A.W. The role of plasminogen,plasminogen activators, and matrix metalloproteinases in primate arterial smooth muscle cell migration. Arterioscler. Thromb. Vasc. Biol. 16:1373-1382, 1996 https://doi.org/10.1161/01.ATV.16.11.1373
  21. Fitzgerald, M., Hayward, I.P., Thomas, A.C., Campbell, G.R., Campbell, J.H. Matrix metalloproteinases can facilitate the heparanase-induced promotion of phenotypic change in vascular smooth muscle cells. Atherosclerosis 145:97-106, 1999 https://doi.org/10.1016/S0021-9150(99)00019-2
  22. Heber, D. Herbs and atherosclerosis.Curr. Atheroscler. Rep. 3:93-96, 2001 https://doi.org/10.1007/s11883-001-0016-9
  23. Yoshie, F., Iizuka, A., Kubo, M., Komatsu, Y., Matsumoto, A., Itakura, H., Takeda, H., Matsumiya, T., Kondo, K. Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Pharmacol. Res. 43:481-488, 2001 https://doi.org/10.1006/phrs.2001.0804
  24. Kim, B.J., Kim, Y.K., Park, W.H., Ko, J.H., Lee, Y.C., Kim, C.H. A water-extract of the Korean traditional formulation Geiji-Bokryung-Hwan reduces atherosclerosis and hypercholesteremia in cholesterol-fed rabbits. Int. Immunopharmacol. 3:723-734, 2003 https://doi.org/10.1016/S1567-5769(03)00073-0
  25. Ha, K.T., Lee, T.K., Kwak, K.H., Kim, J.K., Kim, D.I., Choi, D.Y., Kim, C.H. Inhibitory effect of Cho-Deung-San on human aortic smooth muscle cell migration induced by TNF-$\alpha$alpha through inhibition of matrix metalloproteinase-2 and-9 activity. Vascul. Pharmacol. 41:83-90, 2004 https://doi.org/10.1016/j.vph.2004.05.003
  26. Cha, B.Y., Park, C.J., Lee, D.G., Lee, Y.C., Kim, D.W., Kim, J.D., Seo, W.G., Kim, C.H. Inhibitory effect of methanol extract of Euonymus alatus on matrix metalloproteinase-9. J Ethnopharmacol. 85:163-167, 2003 https://doi.org/10.1016/S0378-8741(02)00373-2
  27. Chung, T.W., Moon, S.K., Lee, Y.C., Kim, J.G., Ko, J.H., Kim, C.H. Enhanced expression of matrix metalloproteinase-9 (MMP-9) by hepatitis B virus infection into liver cells. Arch. Biochem. Biophys. 408:147-154, 2002 https://doi.org/10.1016/S0003-9861(02)00522-2
  28. Ross, R. Cell biology of atherosclerosis, Annu. Rev. Physiol. 57:791-804, 1995 https://doi.org/10.1146/annurev.ph.57.030195.004043
  29. Dollery, C.M., McEwan, J.R., Henney, A.M. Matrix metalloproteinases and cardiovascular disease, Circ. Res. 77:863-868, 1995 https://doi.org/10.1161/01.RES.77.5.863
  30. Mason, D.P., Kenagy, R.D., Hasenstab, D., Bowen-Pope, D.F., Seifert, R.A., Coats, S., Hawkins, S.M., Clowes, A.W. Matrix metalloproteinase-9 overexpression enhances vascular smooth muscle cell migration and alters remodeling in the injured rat carotid artery, Circ. Res. 85:1179-1185, 1999 https://doi.org/10.1161/01.RES.85.12.1179
  31. Pauly, R.R., Passaniti, A., Bilato, C., Monticone, R., Cheng, L., Papadopoulos, N., Gluzband, Y.A., Smith, L., Weinstein, C., Lakatta, E.G. Migration of cultured vascular smooth muscle cells through a basement membrane barrier requires type IV collagenase activity and is inhibited by cellular differentiation, Circ. Res. 75:41-54, 1994 https://doi.org/10.1161/01.RES.75.1.41
  32. Cho, A., Reidy, M.A. Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury, Circ. Res. 91:845-851, 2002 https://doi.org/10.1161/01.RES.0000040420.17366.2E
  33. Huang, H.C., Wang, H.R., Hsieh, L.M. Antiproliferative effect of baicalein, a flavonoid from a Chinese herb, on vascular smooth muscle cell. Eur. J. Pharmacol. 251:91-93, 1994 https://doi.org/10.1016/0014-2999(94)90447-2
  34. Maeda, K., Kuzuya, M., Cheng, X.W., Asai, T., Kanda, S., Tamaya-Mori, N., Sasaki, T., Shibata, T., Iguchi, A. Green tea catechins inhibit the cultured smooth muscle cell invasion through the basement barrier.Atherosclerosis 166:23-30, 2003 https://doi.org/10.1016/S0021-9150(02)00302-7
  35. Kim, D.W., Chung, H.J., Nose, K., Maruyama, I., Tani, T. Preventive effects of a traditional Chinese formulation, Chaihu-jia-Longgu-Muli-tang, on intimal thickening of carotid artery injured by balloon endothelial denudation in rats. J. Pharm. Pharmacol. 54:571-575, 2002 https://doi.org/10.1211/0022357021778691
  36. Tonn, J.C., Kerkau, S., Hanke, A., Bouterfa, H., Mueller, J.G., Wagner, S., Vince, G.H., Roosen, K. Effect of synthetic matrixmetalloproteinase inhibitors on invasive capacity and proliferation of human malignant gliomas in vitro. International journal of cancer 80:764-772, 1999 https://doi.org/10.1002/(SICI)1097-0215(19990301)80:5<764::AID-IJC22>3.0.CO;2-J
  37. Jiang, M.C., Liao, C.F., Lee, P.H. Aspirin inhibits matrix metalloproteinase-2 activity, increases E-cadherin production, and inhibits in vitro invasion of tumor cells. Biochemical and biophysical research communications 282:671-677, 2001 https://doi.org/10.1006/bbrc.2001.4637
  38. Kleiner, D.E., Stetler-Stevenson, W.G. Matrix metalloproteinases and metastasis. Cancer chemotherapy and pharmacology 43:42-51, 1999 https://doi.org/10.1007/s002800051097
  39. Hofmann, C.S., Sonenshein, G.E. Green tea polyphenol epigallocatechin-3 gallate induces apoptosis of proliferating vascular smooth muscle cells via activation of p 53. FASEB J. 17:702-704, 2003 https://doi.org/10.1096/fj.02-0665fje
  40. Miura, Y., Chiba, T., Tomita, I., Koizumi, H., Miura, S., Umegaki, K., Hara, Y., Ikeda, M., Tomita, T. Tea catechins prevent the development of atherosclerosis in apoprotein E-deficient mice. J. Nutr. 131:27-32, 2001 https://doi.org/10.1093/jn/131.1.27
  41. Demeule, M., Brossard, M., Page, M., Gingras, D., Beliveau, R. Matrix metalloproteinase inhibition by green tea catechins. Biochimica et Biophysica Acta 1478:51-60, 2000 https://doi.org/10.1016/S0167-4838(00)00009-1
  42. Chung, T.W., Moon, S.K., Chang, Y.C., Ko, J.H., Lee, Y.C., Cho, G., Kim, S.H., Kim, J.G., Kim, C.H. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J. 18:1670-1681 https://doi.org/10.1096/fj.04-2126com