Skip to main content

Advertisement

SpringerLink
Log in

Roles of Hemodynamic Forces in Vascular Cell Differentiation

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

The pulsatile nature of blood flow is a key stimulus for the modulation of vascular cell differentiation. Within the vascular media, physiologic stress is manifested as cyclic strain, while in the lumen, cells are subjected to shear stress. These two respective biomechanical forces influence the phenotype and degree of differentiation or proliferation of smooth muscle cells and endothelial cells within the human vasculature. Elucidation of the effect of these mechanical forces on cellular differentiation has led to a surge of research into this area because of the implications for both the treatment of atherosclerotic disease and the future of vascular tissue engineering. The use of mechanical force to directly control vascular cell differentiation may be utilized as an invaluable engineering tool in the future. However, an understanding of the role of hemodynamics in vascular cell differentiation and proliferation is critical before application can be realized. Thus, this review will provide a current perspective on the latest research and controversy behind the role of hemodynamic forces for vascular cell differentiation and phenotype modulation. Furthermore, this review will illustrate the application of hemodynamic force for vascular tissue engineering and explicate future directions for research.

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

Similar content being viewed by others

References

  1. Akimoto, S., M. Mitsumata, T. Sasaguri, and Y. Yoshida. Laminar shear stress inhibits vascular endothelial cell proliferation by inducing cyclin-dependent kinase inhibitor p21(Sdil/Cipl/Wafl). Circ. Res. 86:185–190, 2000.

    CAS  PubMed  Google Scholar 

  2. Albinsson, S., I. Nordstrom, and P. Hellstrand. Stretch of the vascular wall induces smooth muscle differentiation by promoting actin polymerization. J. Biol. Chem. 279:34849–34855, 2004.

    Article  CAS  PubMed  Google Scholar 

  3. Ando, J., T. Komatsuda, C. Ishikawa, and A. Kamiya. Fluid shear stress enhanced DNA synthesis in cultured endothelial cells during repair of mechanical denudation. Biorheology 27:675–684, 1990.

    CAS  PubMed  Google Scholar 

  4. Baguneid, M., D. Murray, H. J. Salacinski, B. Fuller, G. Hamilton, M. Walker, and A. M. Seifalian. Shear-stress preconditioning and tissue-engineering-based paradigms for generating arterial substitutes. Biotechnol. Appl. Biochem. 39:151–157, 2004.

    Article  CAS  PubMed  Google Scholar 

  5. Ballermann, B. J., A. Dardik, E. Eng, and A. Liu. Shear stress and the endothelium. Kidney Int. Suppl. 67:S100–S108, 1998.

    Article  CAS  PubMed  Google Scholar 

  6. Birukov, K. G., V. P. Shirinsky, O. V. Stepanova, V. A. Tkachuk, A. W. Hahn, T. J. Resink, and V. N. Smirnov. Stretch affects phenotype and proliferation of vascular smooth muscle cells. Mol. Cell Biochem. 144:131–139, 1995.

    Article  CAS  PubMed  Google Scholar 

  7. Browning, C. L., D. E. Culberson, I. V. Aragon, R. A. Fillmore, J. D. Croissant, R. J. Schwartz, and W. E. Zimmer. The developmentally regulated expression of serum response factor plays a key role in the control of smooth muscle-specific genes. Dev. Biol. 194:18–37, 1998.

    Article  CAS  PubMed  Google Scholar 

  8. Cevallos, M., S. Yan, M. Li, H. Chai, H. Yang, Q. Yao, and C. Chen. Cyclic Strain Induces Expression of Specific Smooth Muscle Cell Markers in Human Endothelial Cells. 38th Annual Meeting of the Association for Academic Surgery. Houston, TX, 2004.

  9. Chapman, G. B., W. Durante, J. D. Hellums, and A. I. Schafer. Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 278:H748–754, 2000.

    Google Scholar 

  10. Chen, X. L., S. E. Varner, A. S. Rao, J. Y. Grey, S. Thomas, C. K. Cook, M. A. Wasserman, R. M. Medford, A. K. Jaiswal, and C. Kunsch. Laminar flow induction of antioxidant response element-mediated genes in endothelial cells. A novel anti-inflammatory mechanism. J. Biol. Chem. 278:703–711, 2003.

    CAS  PubMed  Google Scholar 

  11. Cunningham, J. J., J. J. Linderman, and D. J. Mooney. Externally applied cyclic strain regulates localization of focal contact components in cultured smooth muscle cells. Ann. Biomed. Eng. 30:927–935, 2002.

    Article  PubMed  Google Scholar 

  12. Dardik, A., A. Liu, and B. J. Ballermann. Chronic in vitro shear stress stimulates endothelial cell retention on prosthetic vascular grafts and reduces subsequent in vivo neointimal thickness. J. Vasc. Surg. 29:157–167, 1999.

    CAS  PubMed  Google Scholar 

  13. Dekker, R. J., S. van Soest, R. D. Fontijn, S. Salamanca, P. G. de Groot, E. VanBavel, H. Pannekoek, and A. J. Horrevoets. Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2). Blood 100:1689–1698, 2002.

    Article  CAS  PubMed  Google Scholar 

  14. Duband, J. L., M. Gimona, M. Scatena, S. Sartore, and J. V. Small. Calponin and SM 22 as differentiation markers of smooth muscle: Spatiotemporal distribution during avian embryonic development. Differentiation 55:1–11, 1993.

    Article  CAS  PubMed  Google Scholar 

  15. Gimona, M., D. O. Furst, and J. V. Small. Metavinculin and vinculin from mammalian smooth muscle: Bulk isolation and characterization. J. Muscle Res. Cell Motil. 8:329–341, 1987.

    Article  CAS  PubMed  Google Scholar 

  16. Gloe, T., H. Y. Sohn, G. A. Meininger, and U. Pohl. Shear stress-induced release of basic fibroblast growth factor from endothelial cells is mediated by matrix interaction via integrin alpha(v)beta3. J. Biol. Chem. 277:23453–23458, 2002.

    Article  CAS  PubMed  Google Scholar 

  17. Grainger, D. J., J. C. Metcalfe, A. A. Grace, and D. E. Mosedale. Transforming growth factor-beta dynamically regulates vascular smooth muscle differentiation in vivo. J. Cell Sci. 111:2977–2988, 1998.

    CAS  Google Scholar 

  18. Hamilton, D. W., T. M. Maul, and D. A. Vorp. Characterization of the response of bone marrow-derived progenitor cells to cyclic strain: Implications for vascular tissue-engineering applications. Tissue Eng. 10:361–369, 2004.

    Article  CAS  PubMed  Google Scholar 

  19. Hipper, A., and G. Isenberg. Cyclic mechanical strain decreases the DNA synthesis of vascular smooth muscle cells. Pflugers Arch. 440:19–27, 2000.

    CAS  PubMed  Google Scholar 

  20. Hirschi, K. K., S. A. Rohovsky, and P. A. D’Amore. PDGF, TGF-β, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J. Cell Biol. 141:805–814, 1998.

    Google Scholar 

  21. Hoerstrup, S. P., G. Zund, R. Sodian, A. M. Schnell, J. Grunenfelder, and M. I. Turina. Tissue engineering of small caliber vascular grafts. Eur. J. Cardiothorac. Surg. 20:164–169, 2001.

    Article  CAS  PubMed  Google Scholar 

  22. Imberti, B., D. Seliktar, R. M. Nerem, and A. Remuzzi. The response of endothelial cells to fluid shear stress using a co-culture model of the arterial wall. Endothelium 9:11–23, 2002.

    Article  CAS  PubMed  Google Scholar 

  23. Jockenhoevel, S., G. Zund, S. P. Hoerstrup, A. Schnell, and M. Turina. Cardiovascular tissue engineering: A new laminar flow chamber for in vitro improvement of mechanical tissue properties. ASAIOJ. 48:8–11, 2002.

    Article  Google Scholar 

  24. Kakisis, J. D., C. D. Liapis, and B. E. Sumpio. Effects of cyclic strain on vascular cells. Endothelium 11:17–28, 2004.

    Article  CAS  PubMed  Google Scholar 

  25. Kanda, K., and T. Matsuda. Behavior of arterial wall cells cultured on periodically stretched substrates. Cell Transplant 2:415–484, 1993.

    Google Scholar 

  26. Kashiwada, K., W. Nishida, K. Hayashi, K. Ozawa, Y. Yamanaka, H. Saga, T. Yamashita, M. Tohyama, S. Shimada, K. Sato, and K. Sobue. Coordinate expression of alpha-tropomyosin and caldesmon isoforms in association with phenotypic modulation of smooth muscle cells. J. Biol. Chem. 272:15396–15404, 1997.

    Article  CAS  PubMed  Google Scholar 

  27. Kaushal, S., G. E. Amiel, K. J. Guleserian, O. M. Shapira, T. Perry, F. W. Sutherland, E. Rabkin, A. M. Moran, F. J. Schoen, A. Atala, S. Soker, J. Bischoff, and J. E. Mayer, Jr. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat. Med. 7:1035–1040, 2001.

    Article  CAS  PubMed  Google Scholar 

  28. Kim, B. S., and D. J. Mooney. Scaffolds for engineering smooth muscle under cyclic mechanical strain conditions. J. Biomech. Eng. 122:210–215, 2000.

    Article  CAS  PubMed  Google Scholar 

  29. Kim, B. S., J. Nikolovski, J. Bonadio, and D. J. Mooney. Cyclic mechanical strain regulates the development of engineered smooth muscle tissue. Nat. Biotechnol. 17:979–983, 1999.

    Article  CAS  PubMed  Google Scholar 

  30. Lee, R. T., C. Yamamoto, Y. Feng, S. Potter-Perigo, W. H. Briggs, K. T. Landschulz, T. G. Turi, J. F. Thompson, P. Libby, and T. N. Wight. Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells. J. Biol. Chem. 276:13847–13851, 2001.

    CAS  PubMed  Google Scholar 

  31. Lehoux, S., and A. Tedgui. Cellular mechanics and gene expression in blood vessels. J. Biomech. 36:631–643, 2003.

    Article  PubMed  Google Scholar 

  32. Li, Q., Y. Muragaki, H. Ueno, and A. Ooshima. Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin–angiotensin system and platelet-derived growth factor (PDGF). Hypertens. Res. 20:217–223, 1997.

    CAS  PubMed  Google Scholar 

  33. Ma, Y. H., S. Ling, and H. E. Ives. Mechanical strain increases PDGF-B and PDGF beta receptor expression in vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 265:606–610, 1999.

    Article  CAS  PubMed  Google Scholar 

  34. Mills, I., C. R. Cohen, K. Kamal, G. Li, T. Shin, W. Du, and B. E. Sumpio. Strain activation of bovine aortic smooth muscle cell proliferation and alignment: Study of strain dependency and the role of protein kinase A and C signaling pathways. J. Cell Physiol. 170:228–234, 1997.

    Article  CAS  PubMed  Google Scholar 

  35. Niklason, L. E., J. Gao, W. M. Abbott, K. K. Hirschi, S. Houser, R. Marini, and R. Langer. Functional arteries grown in vitro. Science 284:489–493, 1999.

    CAS  PubMed  Google Scholar 

  36. Niklason, L. E., W. Abbott, J. Gao, B. Klagges, K. K. Hirschi, K. Ulubayram, N. Conroy, R. Jones, A. Vasanawala, S. Sanzgiri, and R. Langer. Morphologic and mechanical characteristics of engineered bovine arteries. J. Vasc. Surg. 33:628–638, 2001.

    Article  CAS  PubMed  Google Scholar 

  37. Nikolovski, J., B. S. Kim, and D. J. Mooney. Cyclic strain inhibits switching of smooth muscle cells to an osteoblast-like phenotype. FASEB J. 17:455–457, 2003.

    CAS  PubMed  Google Scholar 

  38. O’Callaghan, C. J., and B. Williams. Mechanical strain-induced extracellular matrix production by human vascular smooth muscle cells: Role of TGF-beta(1). Hypertension 36:319–324, 2000.

    CAS  PubMed  Google Scholar 

  39. Ott, M. J., and B. J. Ballermann. Shear stress-conditioned, endothelial cell-seeded vascular grafts: Improved cell adherence in response to in vitro shear stress. Surgery 117:334–339, 1995.

    CAS  PubMed  Google Scholar 

  40. Owens, G. K., M. S. Kumar, and B. R. Wamhoff. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol. Rev. 84:767–801, 2004.

    Article  CAS  PubMed  Google Scholar 

  41. Park, J. S., J. S. Chu, C. Cheng, F. Chen, D. Chen, and S. Li. Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells. Biotechnol. Bioeng. 88:359–368, 2004.

    Article  CAS  PubMed  Google Scholar 

  42. Reusch, P., H. Wagdy, R. Reusch, E. Wilson, and H. E. Ives. Mechanical strain increases smooth muscle and decreases nonmuscle myosin expression in rat vascular smooth muscle cells. Circ. Res. 79:1046–1053, 1996.

    CAS  PubMed  Google Scholar 

  43. Seliktar, D., R. M. Nerem, and Z. S. Galis. The role of matrix metalloproteinase-2 in the remodeling of cell-seeded vascular constructs subjected to cyclic strain. Ann. Biomed. Eng. 29:923–934, 2001.

    Article  CAS  PubMed  Google Scholar 

  44. Shi, Q., S. Rafii, M. H. Wu, E. S. Wijelath, C. Yu, A. Ishida, Y. Fujita, S. Kothari, R. Mohle, L. R. Sauvage, M. A. Moore, R. F. Storb, and W. P. Hammond. Evidence for circulating bone marrow-derived endothelial cells. Blood 92:362–367, 1998.

    CAS  PubMed  Google Scholar 

  45. Shields, J. M., R. J. Christy, and V. W. Yang. Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest. J. Biol. Chem. 271:20009–20017, 1996.

    Article  CAS  PubMed  Google Scholar 

  46. Shirota, T., H. He, H. Yasui, and T. Matsuda. Human endothelial progenitor cell-seeded hybrid graft: Proliferative and antithrombogenic potentials in vitro and fabrication processing. Tissue Eng. 9:127–136, 2003.

    Article  CAS  PubMed  Google Scholar 

  47. Singh, T. M., K. Y. Abe, T. Sasaki, Y. J. Zhuang, H. Masuda, and C. K. Zarins. Basic fibroblast growth factor expression precedes flow-induced arterial enlargement. J. Surg. Res. 77:165–173, 1998.

    Article  CAS  PubMed  Google Scholar 

  48. Smith, P. G., R. Moreno, and M. Ikebe. Strain increases airway smooth muscle contractile and cytoskeletal proteins in vitro. Am. J. Physiol. 272:L20–27, 1997.

    Google Scholar 

  49. Stegemann, J. P., and R. M. Nerem. Phenotype modulation in vascular tissue engineering using biochemical and mechanical stimulation. Ann. Biomed. Eng. 31:391–402, 2003.

    Article  PubMed  Google Scholar 

  50. Sterpetti, A. V., A. Cucina, L. Santoro, B. Cardillo, and A. Cavallaro. Modulation of arterial smooth muscle cell growth by haemodynamic forces. Eur. J. Vasc. Surg. 6:16–20, 1992.

    CAS  PubMed  Google Scholar 

  51. Tock, J., V. Van Putten, K. R. Stenmark, and R. A. Nemenoff. Induction of SM-alpha-actin expression by mechanical strain in adult vascular smooth muscle cells is mediated through activation of JNK and p38 MAP kinase. Biochem. Biophys. Res. Commun. 301:1116–1121, 2003.

    Article  CAS  PubMed  Google Scholar 

  52. Van Gieson, E. J., W. L. Murfee, T. C. Skalak, and R. J. Price. Enhanced smooth muscle cell coverage of microvessels exposed to increased hemodynamic stresses in vivo. Circ. Res. 92:929–936, 2003.

    Article  CAS  Google Scholar 

  53. Wang, H., S. Yan, M. Li, H. Chai, H. Yang, Q. Yao, and C. Chen. Shear stress induces endothelial cell differentiation from mouse embryo mesenchymal progenitor cells. J. Surg. Res. 121:274, 2004.

    Article  Google Scholar 

  54. Wasserman, S. M., and J. N. Topper. Adaptation of the endothelium to fluid flow: In vitro analyses of gene expression and in vivo implications. Vasc. Med. 9:35–45, 2004.

    Article  PubMed  Google Scholar 

  55. Wasserman, S. M., F. Mehraban, L. G. Komuves, R. B. Yang, J. E. Tomlinson, Y. Zhang, F. Spriggs, and J. N. Topper. Gene expression profile of human endothelial cells exposed to sustained fluid shear stress. Physiol. Genomics 12:13–23, 2002.

    CAS  PubMed  Google Scholar 

  56. Wilson, E., K. Sudhir, and H. E. Ives. Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions. J. Clin. Invest. 96:2364–2372, 1995.

    CAS  PubMed  Google Scholar 

  57. Yamamoto, K., T. Takahashi, T. Asahara, N. Ohura, T. Sokabe, A. Kamiya, and J. Ando. Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress. J. Appl. Physiol. 95:2081–2088, 2003.

    Google Scholar 

  58. Zeidan, A., I. Nordstrom, S. Albinsson, U. Malmqvist, K. Sward, and P. Hellstrand. Stretch-induced contractile differentiation of vascular smooth muscle: Sensitivity to actin polymerization inhibitors. Am. J. Physiol. Cell Physiol. 284:C1387–1396, 2003.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, 77030

    Gordon M. Riha, Peter H. Lin, Alan B. Lumsden, Qizhi Yao & Changyi Chen

Authors
  1. Gordon M. Riha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter H. Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan B. Lumsden
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qizhi Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Changyi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Changyi Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Riha, G.M., Lin, P.H., Lumsden, A.B. et al. Roles of Hemodynamic Forces in Vascular Cell Differentiation. Ann Biomed Eng 33, 772–779 (2005). https://doi.org/10.1007/s10439-005-3310-9

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-005-3310-9

Keywords

Search

Navigation