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Expression of Heparan Sulphate N-deacetylase/N-sulphotransferase by Vascular Smooth Muscle Cells

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Abstract

Heparan sulphate is an important mediator in determining vascular smooth muscle cell (SMC) phenotype. The sulphation pattern of the heparan sulphate chains is critical to their function. We have examined the initial step in the biosynthesis of the sulphated domains mediated by the enzyme heparan sulphate N-deacetylase/N-sulphotransferase (NDST). Rabbit aortic SMC in primary culture exhibited NDST enzyme activity and expressed NDST-1 in their Golgi apparatus, with maximal expression in SMC 2 days after dispersal in primary culture confirmed by Western blot analysis. Endothelial cells, macrophages and fibroblasts expressed NDST-1 but had generally less intense staining than SMC, although SMC expression decreased with culture. The uninjured rat aorta also showed widespread expression of NDST-1. After balloon de-endothelialisation, NDST-1 could not be detected in SMC of the neointima in the early stages of neointimal formation, but was re-expressed at later time points (after 12 weeks). In human coronary arteries, SMC of the media and the diffuse intimal thickening expressed NDST-1, while SMC in the atherosclerotic plaque were negative for NDST-1. We conclude that SMC may regulate their heparan sulphate sulphation at the level of expression of the enzyme heparan sulphate NDST in a manner related to their phenotypic state.

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References

  • Aikawa J, Esko J (1999) Molecular cloning and expression of a third member of the heparan sulfate/heparin GlcNac N-deacetylase/ N-sulfotransferase family. J Biol Chem 274: 2690–2695.

    Article  CAS  PubMed  Google Scholar 

  • Aikawa J, Grobe K, Tsujimoto M, Esko J (2001) Multiple isozymes of heparan sulfate/heparin GlcNAc N-deacetylase/GlcN N-sulfotransferase. J Biol Chem 276: 5876–5882.

    Article  CAS  PubMed  Google Scholar 

  • Bingley JA, Hayward IP, Campbell GR, Campbell JH (2001) Relationship of glycosaminoglycan and matrix changes to vascular smooth muscle cell phenotype modulation in rabbit arteries following acute injury. J Vasc Surg 33: 155–164.

    Article  CAS  PubMed  Google Scholar 

  • Bingley JA, Hayward IP, Campbell JH, Campbell GR(1998) Arterial heparan sulfate proteoglycans inhibit vascular smooth muscle cell proliferation and phenotype change in vitro and neointimal formation in vivo. J Vasc Surg 28: 308–318.

    Article  CAS  PubMed  Google Scholar 

  • Campbell GR, Campbell JH (1987) Phenotypic modulation of smooth muscle cells in primary culture. In: Campbell JH, Campbell GR, eds. Vascular Smooth Muscle in Culture. Boca Raton: CRC Press, pp 39–56.

    Google Scholar 

  • Campbell JH, Campbell GR (1993) Culture techniques and their applications to studies of vascular smooth muscle. Clin Sci 85: 510–513.

    Google Scholar 

  • Campbell JH, Rennick RE, Kalevitch SG, Campbell GR (1992) Heparan sulphate-degrading enzymes induce modulation of smooth muscle phenotype. Exp Cell Res 200: 156–167.

    Article  CAS  PubMed  Google Scholar 

  • Castellot JJ, Wright TC, Karnovsky MJ (1987) Regulation of vascular smooth muscle cell growth by heparin and heparan sulfate. Sem Thromb Haem 13: 489–503.

    Article  CAS  Google Scholar 

  • Clowes AW, Karnovsky MJ (1977) Suppression by heparin of smooth muscle cell proliferation in injured arteries. Nature 265: 625–626.

    Article  CAS  PubMed  Google Scholar 

  • Dalferes ER, Radhakrishnamurthy B, Ruiz H, Berenson GS (1987) Composition of proteoglycans from human atherosclerotic lesions. Exp Molec Pathol 47: 363–376.

    Article  CAS  Google Scholar 

  • David G, Bai XM, Van der Schueren B, Cassiman JJ, Van den Berghe H (1992) Developmental changes in heparan sulfate expression: In situ detection with mAbs. J Cell Biol 119: 961–975.

    Article  CAS  PubMed  Google Scholar 

  • Esko JD, Lindahl U (2001) Molecular diversity of heparan sulfate. J Clin Invest 108: 169–173.

    CAS  PubMed  Google Scholar 

  • Fan G, Xiao L, Cheng L,Wang X, Sun B, Gengxi H (2000) Targeted disruption of NDST-1 gene leads to pulmonary hypoplasia and neonatal respiratory distress in mice. FEBS Lett 467: 7–11.

    Article  CAS  PubMed  Google Scholar 

  • Fritze LMS, Reilly CF, Rosenberg RD (1985) An antiproliferative heparan sulfate species produced by postconfluent smooth muscle cells. J Cell Biol 100: 1041–1049.

    Article  CAS  PubMed  Google Scholar 

  • Girjes AA, Keriakous D, Hayward IP, Campbell GR, Campbell JH (2001) Cloning of genes differentially regulated during change in vascular smooth muscle phenotype. FEBS Lett 509: 341–342.

    Article  CAS  PubMed  Google Scholar 

  • Hein M, Fischer J, Kim DK, Hein L, Pratt RE (1996) Vascular smooth muscle cell phenotype influences glycosaminoglycan composition and growth effects of extracellular matrix. J Vasc Res 33: 433–441.

    CAS  PubMed  Google Scholar 

  • Hollmann J, Schmidt A, von Bassewitz D-B, Buddecke E (1989) Relationship of sulfated glycosaminoglycans and cholesterol content in normal and atherosclerotic human aorta. Arteriosclerosis 9: 154–158.

    CAS  PubMed  Google Scholar 

  • Hoover RL, Rosenberg R, Haering W, Karnovsky MJ (1980) Inhibition of rat arterial smooth muscle cell proliferation by heparin II. In vitro studies. Circ Res 47: 578–583.

    CAS  PubMed  Google Scholar 

  • Humphries DE, Sullivan BM, Aleixo MD, Stow JL (1997) Localization of human heparan glycosaminyl N-deacetylase/N-sulphotransferase to the trans-Golgi network. Biochem J 325: 351–357.

    CAS  PubMed  Google Scholar 

  • Humphries DE, Wong GW, Friend DS, Gurish MF, Qiu W, Huang C, Sharpe AH, Stevens RL (1999) Heparin is essential for the storage of specific granule proteases in mast cells. Nature 400: 769–772.

    Article  CAS  PubMed  Google Scholar 

  • Li Z-Y, Hirayoshi K, Suzuki Y (2000) Expression of N-deacetylase/ sulfotransferase and 3-O-sulfotransferase in rat alveolar type II cells. Am J Physiol Lung Cell Mol Physiol 279: L292–L301.

    CAS  PubMed  Google Scholar 

  • Lindahl U, Kusche M, Lidholt K, Oscarrson LG (1989) Biosynthesis of heparin and heparan sulfate. In: Lane DA, Lindahl U, eds. Heparin. London: Arnold, pp 548–574.

    Google Scholar 

  • Manderson JA, Mosse PRL, Safstrom JA, Young SB, Campbell GR (1989) Balloon catheter injury to rabbit carotid artery. I. Changes in smooth muscle cell phenotype. Arteriosclerosis 9: 289–298.

    CAS  PubMed  Google Scholar 

  • Mosse PRL, Campbell GR, Wang ZL, Campbell JH (1985) Smooth muscle phenotypic expression in human carotid arteries. Lab Invest 53: 556–562.

    CAS  PubMed  Google Scholar 

  • Pikas DS, Eriksson I, Kjellén L (2000) Overexpression of different isoforms of glucosaminyl N-deacetylase/N-sulfotransferase results in distinct heparan sulfate N-sulfation patterns. Biochemistry 39: 4552–4558.

    Article  CAS  PubMed  Google Scholar 

  • Radhakrishnamurthy B, Srinivasan SR, Eberle K, Ruiz H, Dalferes ER, Sharma C, Berenson GS (1988) Composition of proteoglycans synthesised by rabbit aortic smooth muscle cells explants in culture and effect of experimental atherosclerosis. Biochim Biophys Acta 964: 231–243.

    CAS  PubMed  Google Scholar 

  • Ringvall M, Ledin J, Holmborn K, van Kuppevelt T, Ellin F, Eriksson I, Olofsson AM, Kjellen L, Forsberg E (2000) Defective heparan sulfate biosynthesis and neonatal lethality in mice lacking N-deacetylase/ N-sulfotransferase-1. J Biol Chem 275: 25926–25930.

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg RD, Shworak NW, Liu J, Schwartz JJ, Zhang L (1997) Heparan sulfate proteoglycans of the cardiovascular system. J Clin Invest 99: 2062–2070.

    Article  CAS  PubMed  Google Scholar 

  • Salmivirta M, Lidholt K, Lindahl U (1996) Heparan sulfate: A piece of information. FASEB J 10: 1270–1279.

    CAS  PubMed  Google Scholar 

  • Schmidt A, Buddecke E (1990) Bovine aortic smooth muscle cells synthesize two functionally different proteoheparan sulphate species. Exp Cell Res 189: 269–275.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt A, Lemming G, Yoshida K, Buddecke E (1992) Molecular organisation and antiproliferative domains of arterial tissue heparan sulfate. Eur J Cell Biol 59: 322–328.

    CAS  PubMed  Google Scholar 

  • Toma L, Berninsone P, Hirschberg CB (1998) The putative heparinspecific N-acetylglucosaminyl N-deacetylase/N-sulfotransferase also occurs in non-heparin-producing cells. J Biol Chem 273: 22458–22465.

    Article  CAS  PubMed  Google Scholar 

  • Wight TN (1989) Cell Biology of Arterial Proteoglycans. Arteriosclerosis 9: 1–20.

    CAS  PubMed  Google Scholar 

  • Williams SP, Mason RM (1991) Modulation of proteoglycan synthesis by bovine vascular smooth muscle cell proliferation and treatment with heparin. Arch Biochem Biophys 287: 386–396.

    Article  CAS  PubMed  Google Scholar 

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Bingley, J.A., Hayward, I.P., Girjes, A.A. et al. Expression of Heparan Sulphate N-deacetylase/N-sulphotransferase by Vascular Smooth Muscle Cells. Histochem J 34, 131–137 (2002). https://doi.org/10.1023/A:1020938430120

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