Skip to main content
Log in

Effects of Fluid Shear Stress on a Distinct Population of Vascular Smooth Muscle Cells

  • Published:
Cellular and Molecular Bioengineering Aims and scope Submit manuscript

Abstract

Vascular smooth muscle cells (SMCs) are a major cell type involved in vascular remodeling. The various developmental origins of SMCs such as neural crest and mesoderm result in the heterogeneity of SMCs, which plays an important role in vascular remodeling and disease development. Upon vascular injury, SMCs are exposed to blood flow and subjected to fluid shear stress. Previous studies have shown that fluid shear stress inhibits SMC proliferation. However, the effect of shear stress on the subpopulation of SMCs from specific developmental origin and vascular bed is not well understood. Here we investigated how shear stress regulates human aortic SMCs positive for neural crest markers. DNA microarray analysis showed that shear stress modulates the expression of genes involved in cell proliferation, matrix synthesis, cell signaling, transcription and cytoskeleton organization. Further studies demonstrated that shear stress induced SMC proliferation and cyclin D1, downregulated cell cycle inhibitor p21, and activated Akt pathway. Inhibition of PI-3 kinase blocked these shear stress-induced changes. These results suggest that SMCs with neural crest characteristics may respond to shear stress in a different manner. This finding has significant implications in the remodeling and disease development of blood vessels.

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

Access this article

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

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Bauters, C., and J. M. Isner. The biology of restenosis. Prog. Cardiovasc. Dis. 40(2):107–116, 1997.

    Article  Google Scholar 

  2. Bergwerff, M., et al. Neural crest cell contribution to the developing circulatory system: implications for vascular morphology? Circ. Res. 82(2):221–231, 1998.

    Google Scholar 

  3. Cappadona, C., et al. Phenotype dictates the growth response of vascular smooth muscle cells to pulse pressure in vitro. Exp. Cell Res. 250(1):174–186, 1999.

    Article  Google Scholar 

  4. Chang, M. W., et al. Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty. J. Clin. Invest. 96(5):2260–2268, 1995.

    Article  Google Scholar 

  5. Chang, F., et al. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 17(3):590–603, 2003.

    Article  Google Scholar 

  6. Chiu, J. J., and S. Chien. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol. Rev. 91(1):327–387, 2011.

    Article  Google Scholar 

  7. Chiu, J. J., et al. Mechanisms of induction of endothelial cell E-selectin expression by smooth muscle cells and its inhibition by shear stress. Blood 110(2):519–528, 2007.

    Article  Google Scholar 

  8. DeBakey, M. E., and D. H. Glaeser. Patterns of atherosclerosis: effect of risk factors on recurrence and survival-analysis of 11, 890 cases with more than 25-year follow-up. Am. J. Cardiol. 85(9):1045–1053, 2000.

    Article  Google Scholar 

  9. Fung, Y. C. Biodynamics. New York Inc.: Springer-Verlag, pp. 77–85, 1984.

    Google Scholar 

  10. Giddens, D. P., C. K. Zarins, and S. Glagov. The role of fluid mechanics in the localization and detection of atherosclerosis. J. Biomech. Eng. 115(4B):588–594, 1993.

    Article  Google Scholar 

  11. Hirschi, K. K., and M. W. Majesky. Smooth muscle stem cells. Anat. Rec. A Discov. Mol. Cell Evol. Biol. 276(1):22–33, 2004.

    Article  Google Scholar 

  12. Jiang, X., et al. Fate of the mammalian cardiac neural crest. Development 127(8):1607–1616, 2000.

    Google Scholar 

  13. Kohler, T. R., et al. Increased blood flow inhibits neointimal hyperplasia in endothelialized vascular grafts. Circ. Res. 69(6):1557–1565, 1991.

    Google Scholar 

  14. Kraiss, L. W., et al. Shear stress regulates smooth muscle proliferation and neointimal thickening in porous polytetrafluoroethylene grafts. Arterioscler. Thromb. 11(6):1844–1852, 1991.

    Article  Google Scholar 

  15. Kurpinski, K., et al. Regulation of vascular smooth muscle cells and mesenchymal stem cells by mechanical strain. Mol. Cell Biomech. 3(1):21–34, 2006.

    MATH  Google Scholar 

  16. Li, C., and Q. Xu. Mechanical stress-initiated signal transductions in vascular smooth muscle cells. Cell Signal 12(7):435–445, 2000.

    Article  Google Scholar 

  17. Li, S., et al. Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. J. Clin. Invest. 103(8):1141–1150, 1999.

    Article  Google Scholar 

  18. Li, S., et al. Innate diversity of adult human arterial smooth muscle cells: cloning of distinct subtypes from the internal thoracic artery. Circ. Res. 89(6):517–525, 2001.

    Article  Google Scholar 

  19. Libby, P., and H. Tanaka. The molecular bases of restenosis. Prog. Cardiovasc. Dis. 40(2):97–106, 1997.

    Article  Google Scholar 

  20. Majesky, M. W. Developmental basis of vascular smooth muscle diversity. Arterioscl. Throm. Vasc. Biol. 27(6):1248–1258, 2007.

    Article  Google Scholar 

  21. Martin, K.A., et al. The mTOR/p70 S6K1 pathway regulates vascular smooth muscle cell differentiation. Am. J. Physiol. Cell Physiol. 286(3):C507–C517, 2004.

    Article  Google Scholar 

  22. Nakamura, T., M. C. Colbert, and J. Robbins. Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system. Circ. Res. 98(12):1547–1554, 2006.

    Article  Google Scholar 

  23. Owens, G. K. Regulation of differentiation of vascular smooth muscle cells. Physiol. Rev. 75(3):487–517, 1995.

    Google Scholar 

  24. Park, J., et al. Differential effects of equiaxial and uniaxial strains on mesenchymal stem cells. Biotechnol. Bioeng. 88(3):359–368, 2004.

    Article  Google Scholar 

  25. Qi, Y. X., et al. PDGF-BB and TGF-β1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress. Proc. Natl Acad. Sci. USA. 108(5):1908–1913, 2011.

    Article  Google Scholar 

  26. Regan, C. P., et al. Molecular mechanisms of decreased smooth muscle differentiation marker expression after vascular injury. J. Clin. Invest. 106(9):1139–1147, 2000.

    Article  Google Scholar 

  27. Ross, R. Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 340(2):115–126, 1999.

    Article  Google Scholar 

  28. Shigematsu, K., et al. Direct and indirect effects of pulsatile shear stress on the smooth muscle cell. Int. Angiol. 19(1):39–46, 2000.

    Google Scholar 

  29. Shiojima, I., and K. Walsh. Role of Akt signaling in vascular homeostasis and angiogenesis. Circ. Res. 90(12):1243–1250, 2002.

    Article  Google Scholar 

  30. Stabile, E., et al. Akt controls vascular smooth muscle cell proliferation in vitro and in vivo by delaying G1/S exit. Circ. Res. 93(11):1059–1065, 2003.

    Article  Google Scholar 

  31. Sterpetti, A. V., et al. Shear stress modulates the proliferation rate, protein synthesis, and mitogenic activity of arterial smooth muscle cells. Surgery 113(6):691–699, 1993.

    Google Scholar 

  32. Tanner, F. C., et al. Differential effects of the cyclin-dependent kinase inhibitors p27(Kip1), p21(Cip1), and p16(Ink4) on vascular smooth muscle cell proliferation. Circulation 101(17):2022–2025, 2000.

    Google Scholar 

  33. Thyberg, J. Differentiated properties and proliferation of arterial smooth muscle cells in culture. Int. Rev. Cytol. 169(183):183–265, 1996.

    Article  Google Scholar 

  34. Tsai, M. C., et al. Shear stress induces synthetic-to-contractile phenotypic modulation in smooth muscle cells via peroxisome proliferator-activated receptor α/δ activations by prostacyclin released by sheared endothelial cells. Circ. Res. 105(5):471–480, 2009.

    Article  Google Scholar 

  35. Ueba, H., M. Kawakami, and T. Yaginuma. Shear stress as an inhibitor of vascular smooth muscle cell proliferation. Role of transforming growth factor-β1 and tissue-type plasminogen activator. Arterioscler. Thromb. Vasc. Biol. 17(8):1512–1516, 1997.

    Article  Google Scholar 

  36. Wang, D. M., and J. M. Tarbell. Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells. J. Biomech. Eng. 117(3):358–363, 1995.

    Article  Google Scholar 

Download references

Acknowledgments

We thank Alex Hsiao, Ryan Hoshi and Mike Ichikawa for their excellent assistance in the experiments. This work was supported in part by grants HL083900 and EB012240 from National Institute of Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Song Li.

Additional information

Associate Editors John Shyy and Yingxiao Wang oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hsu, S., Chu, J.S., Chen, F.F. et al. Effects of Fluid Shear Stress on a Distinct Population of Vascular Smooth Muscle Cells. Cel. Mol. Bioeng. 4, 627–636 (2011). https://doi.org/10.1007/s12195-011-0205-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-011-0205-8

Keywords

Navigation