Skip to main content

Advertisement

SpringerLink
Log in

Smooth Muscle Specific Deletion of Ndst1 Leads to Decreased Vessel Luminal Area and No Change in Blood Pressure in Conscious Mice

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Heparan sulfate proteoglycans are abundant matrix and membrane molecules. Smooth muscle specific deletion of one heparan sulfate biosynthetic enzyme, N-deacetylase-N-sulfotransferase1 leads to decreased vascular smooth muscle cell proliferation, and vascular wall thickness. We hypothesized that this may lead to changes in blood pressure in conscious mice. Blood pressure was measured via telemetry in SM22αCre+Ndst1−/−(n = 4) and wild type (n = 8) mice. Aorta and thoracodorsal artery luminal area is significantly smaller in SM22αCre+Ndst1−/− (n = 4–8, P = 0.02, P = 0.0002) compared to wild type (n = 7) mice. Diurnal differences were observed in both cohorts for systolic, diastolic, mean arterial blood pressure, and heart rate (P < 0.001 from T test). No significant differences were found in the above parameters between the cohorts in either light or dark times using a linear mixed model. In conclusion, deletion of N-deacetylase-N-sulfotransferase1 in smooth muscle did not influence any of the blood pressure parameters measured despite significant decrease in aorta and thoracodorsal artery luminal area.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Esko, J. D., & Selleck, S. B. (2002). Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annual Review of Biochemistry, 71, 435–471.

    Article  PubMed  CAS  Google Scholar 

  2. Bishop, J. R., Schuksz, M., & Esko, J. D. (2007). Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature, 446(7139), 1030–1037.

    Article  PubMed  CAS  Google Scholar 

  3. Bernfield, M., Gotte, M., Park, P. W., Reizes, O., Fitzgerald, M. L., Lincecum, J., & Zako, M. (1999). Functions of cell surface heparan sulfate proteoglycans. Annual Review of Biochemistry, 68, 729–777.

    Article  PubMed  CAS  Google Scholar 

  4. Olsson, A.-K., Dimberg, A., Kreuger, J., & Claesson-Welsh, L. (2006). VEGF receptor signalling? In control of vascular function. Nature Reviews Molecular Cell Biology, 7(5), 359–371.

    Article  PubMed  CAS  Google Scholar 

  5. Iozzo, R. V., & San Antonio, J. D. (2001). Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena. Journal of Clinical Investigation, 108(3), 349–355.

    PubMed  CAS  Google Scholar 

  6. Jakobsson, L., Kreuger, J., Holmborn, K., Lundin, L., Eriksson, I., Kjellen, L., & Claesson-Welsh, L. (2006). Heparan sulfate in trans potentiates VEGFR-mediated angiogenesis. Developmental Cell, 10(5), 625–634.

    Article  PubMed  CAS  Google Scholar 

  7. Kirn-Safran, C. B., D’Souza, S. S., & Carson, D. D. (2008). Heparan sulfate proteoglycans and their binding proteins in embryo implantation and placentation. Seminars in Cell & Developmental Biology, 19(2), 187–193.

    Article  CAS  Google Scholar 

  8. Kirkpatrick, C. A., & Selleck, S. B. (2007). Heparan sulfate proteoglycans at a glance. Journal of Cell Science, 120(Pt 11), 1829–1832.

    Article  PubMed  CAS  Google Scholar 

  9. Rudd. T.R. and Yates, E.A. (2012). A highly efficient tree structure for the biosynthesis of heparan sulfate accounts for the commonly observed disaccharides and suggests a mechanism for domain synthesis. Molecular BioSystems.

  10. Adhikari, N., Basi, D. L., Townsend, D., Rusch, M., Mariash, A., Mullegama, S., Watson, A., Larson, J., Tan, S., Lerman, B., Esko, J. D., Selleck, S. B., & Hall, J. L. (2010). Heparan sulfate Ndst1 regulates vascular smooth muscle cell proliferation, vessel size and vascular remodeling. Journal of Molecular and Cellular Cardiology, 49(2), 287–293.

    Article  PubMed  CAS  Google Scholar 

  11. Adhikari, N., Rusch, M., Mariash, A., Li, Q., Selleck, S. B., & Hall, J. L. (2008). Alterations in heparan sulfate in the vessel in response to vascular injury in the mouse. Journal of Cardiovascular Translational Research, 1(3), 236–240.

    Article  PubMed  Google Scholar 

  12. Zhao, X., Ho, D., Gao, S., Hong, C., Vatner, D.E., Vatner, S.F. (2011) Arterial Pressure Monitoring in Mice, in Current Protocols in Mouse Biology. Wiley

  13. Desjardins, F., Lobysheva, I., Pelat, M., Gallez, B., Feron, O., Dessy, C., & Balligand, J.-L. (2008). Control of blood pressure variability in caveolin-1-deficient mice: role of nitric oxide identified in vivo through spectral analysis. Cardiovascular Research, 79(3), 527–536.

    Article  PubMed  CAS  Google Scholar 

  14. Kramer, K., & Kinter, L. B. (2003). Evaluation and applications of radiotelemetry in small laboratory animals. Physiological Genomics, 13(3), 197–205.

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Ringvall, M., Ledin, J., Holmborn, K., van Kuppevelt, T., Ellin, F., Eriksson, I., Olofsson, A. M., Kjellen, L., & Forsberg, E. (2002). Defective heparan sulfate biosynthesis and neonatal lethality in mice lacking N-deacetylase/N-sulfotransferase-1. Journal of Biological Chemistry, 75, 25926–25930.

    Google Scholar 

  17. Forsberg, E., & Kjellen, L. (2001). Heparan sulfate: lessons from knockout mice. The Journal of Clinical Investigation, 108(2), 175–180.

    PubMed  CAS  Google Scholar 

  18. Francis, D.J., Parish, C.R., McGarry, M., Santiago, F.S., Lowe, H.C., Brown, K.J., Bingley, J.A., Hayward, I.P., Cowden, W.B., Campbell, J.H., Campbell, G.R., Chesterman, C.N., Khachigian, L.M. (2003). Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88: phosphomannopentaose sulfate directly binds FGF-2, blocks cellular signaling, and inhibits proliferation. 92(8): p. e70.

  19. Grobe, K., Inatani, M., Pallerla, S. R., Castagnola, J., Yamaguchi, Y., & Esko, J. D. (2005). Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function. Development, 132, 3777–3786.

    Article  PubMed  CAS  Google Scholar 

  20. Kinnunen, T., Huang, Z., Townsend, J., Gatdula, M. M., Brown, J. R., Esko, J. D., & Turnbull, J. E. (2005). Heparan 2-O-sulfotransferase, hst-2, is essential for normal cell migration in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 102(5), 1507–1512.

    Article  PubMed  CAS  Google Scholar 

  21. Pan, Y., Woodbury, A., Esko, J. D., Grobe, K., & Zhang, X. (2006). Heparan sulfate biosynthetic gene Ndst1 is required for FGF signaling in early lens development. Development, 133(24), 4933–4944.

    Article  PubMed  CAS  Google Scholar 

  22. Pallerla, S. R., Pan, Y., Zhang, X., Esko, J. D., & Grobe, K. (2007). Heparan sulfate Ndst1 gene function variably regulates multiple signaling pathways during mouse development. Developmental Dynamics, 236(2), 556–563.

    Article  PubMed  CAS  Google Scholar 

  23. Wang, L., Fuster, M., Sriramarao, P., & Esko, J. D. (2005). Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses. Nature Immunology, 6(9), 902–910.

    Article  PubMed  CAS  Google Scholar 

  24. Lepore, J. J., Cheng, L., Lu, M. M., Mericko, P. A., Morrisey, E. E., & Parmacek, M. S. (2005). High-efficiency somatic mutagenesis in smooth muscle cells and cardiac myocytes in SM22alpha-Cre transgenic mice. Genesis, 41(4), 179–184.

    Article  PubMed  CAS  Google Scholar 

  25. Frutkin, A. D., Shi, H., Otsuka, G., Leveen, P., Karlsson, S., & Dichek, D. A. (2006). A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre. Journal of Molecular and Cellular Cardiology, 41(4), 724–731.

    Article  PubMed  CAS  Google Scholar 

  26. Grobe, K., Inatani, M., Pallerla, S. R., Castagnola, J., Yamaguchi, Y., & Esko, J. D. (2005). Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function. Development, 132(16), 3777–3786.

    Article  PubMed  CAS  Google Scholar 

  27. Franklin, S. S., Larson, M. G., Khan, S. A., Wong, N. D., Leip, E. P., Kannel, W. B., & Levy, D. (2001). Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study. Circulation, 103(9), 1245–1249.

    PubMed  CAS  Google Scholar 

  28. Gillum, R. F. (1987). The association of body fat distribution with hypertension, hypertensive heart disease, coronary heart disease, diabetes and cardiovascular risk factors in men and women aged 18–79 years. Journal of Chronic Diseases, 40(5), 421–428.

    Article  PubMed  CAS  Google Scholar 

  29. Levy, O., Dayan, T., & Kronfeld-Schor, N. (2007). The Relationship between the Golden Spiny Mouse Circadian System and its diurnal activity: an experimental field enclosures and laboratory study. Chronobiology International, 24(4), 599–613.

    Article  PubMed  Google Scholar 

  30. Pallerla, S. R., Lawrence, R., Lewejohann, L., Pan, Y., Fischer, T., Schlomann, U., Zhang, X., Esko, J. D., & Grobe, K. (2008). Altered heparan sulfate structure in mice with deleted NDST3 gene function. Journal of Biological Chemistry, 283(24), 16885–16894.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota, 6-242 NHH, 312 Church St SE, Minneapolis, MN, 55455, USA

    Kim Ramil C. Montaniel, Cassandra Graham, Marjorie Carlson, William Zeng, Orien Zeng, Jennifer L. Hall & Neeta Adhikari

  2. Robert M Berne Cardiovascular Research Center, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA

    Marie Billaud & Brant E. Isakson

  3. Division of Biostatistics, University of Minnesota, Minneapolis, MN, 55405, USA

    Sun K. Kim & Wei Pan

Authors
  1. Kim Ramil C. Montaniel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie Billaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cassandra Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sun K. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marjorie Carlson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. William Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Orien Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wei Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Brant E. Isakson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jennifer L. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Neeta Adhikari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neeta Adhikari.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Montaniel, K.R.C., Billaud, M., Graham, C. et al. Smooth Muscle Specific Deletion of Ndst1 Leads to Decreased Vessel Luminal Area and No Change in Blood Pressure in Conscious Mice. J. of Cardiovasc. Trans. Res. 5, 274–279 (2012). https://doi.org/10.1007/s12265-012-9369-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-012-9369-4

Keywords

Search

Navigation