Skip to main content
SpringerLink
Log in

Hydraulic Conductivity of Endothelial Cell-Initiated Arterial Cocultures

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

Abstract

This study describes cocultures of arterial smooth muscle cells (SMCs) and endothelial cells (ECs) and the influences of their heterotypic interactions on hydraulic conductivity (L p ), an important transport property. A unique feature of these cocultures is that ECs were first grown to confluence and then SMCs were inoculated. Bovine aortic smooth muscle cells and bovine aortic endothelial cells (BAECs) were cocultured on Transwell Permeable Supports, and then exposed to a pressure-driven transmural flow. L p across each culture was measured using a bubble tracking apparatus that determined water flux (J v ). Our results indicate that arterial L p is significantly modulated by EC–SMC proximity, and serum content in culture. The L p of cocultures was also compared to the predictions of a resistances-in-series model to distinguish the contributions of heterotypic interactions between SMCs and ECs. Conditions that lead to significantly reduced coculture L p , compared to BAEC monoculture controls, have been uncovered and the lowest L p in the literature for an in vitro system are reported. In addition, VE-cadherin immunostaining of intact BAEC monolayers in each culture configuration reveals that EC–SMC proximity on a porous membrane has a dramatic influence on EC morphology patterns. The cocultures with the lowest L p have ECs with significantly elongated morphology. Confocal imaging indicates that there are no direct EC–SMC contacts in coculture.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  1. Aiello, V. D., P. S. Gutierrez, M. J. Chaves, A. A. Lopes, M. L. Higuchi, et al. Morphology of the internal elastic lamina in arteries from pulmonary hypertensive patients: a confocal laser microscopy study. Mod. Pathol. 16:411–416, 2003.

    Article  PubMed  Google Scholar 

  2. Alexander, J. S., W. F. Patton, B. W. Christman, L. L. Cuiper, and F. R. Haselton. Platelet-derived lysophosphatidic acid decreases endothelial permeability in vitro. Am. J. Physiol. 274:H115–H122, 1998.

    CAS  PubMed  Google Scholar 

  3. Buschmann, I., and W. Schaper. Arteriogenesis versus angiogenesis: two mechanisms of vessel growth. News Physiol. Sci. 14:121–125, 1999.

    PubMed  Google Scholar 

  4. Cancel, L. M., A. Fitting, and J. M. Tarbell. In vitro study of LDL transport under pressurized (convective) conditions. Am. J. Physiol. Heart Circ. Physiol. 293:H126–H132, 2007.

    Article  CAS  PubMed  Google Scholar 

  5. Castellot, Jr., J. J., M. J. Karnovsky, and B. M. Spiegelman. Potent stimulation of vascular endothelial cell growth by differentiated 3T3 adipocytes. Proc. Natl. Acad. Sci. U. S. A. 77:6007–6011, 1980.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Chang, Y. S., J. A. Yaccino, S. Lakshminarayanan, J. A. Frangos, and J. M. Tarbell. Shear-induced increase in hydraulic conductivity in endothelial cells is mediated by a nitric oxide-dependent mechanism. Arterioscler. Thromb. Vasc. Biol. 20:35–42, 2000.

    Article  CAS  PubMed  Google Scholar 

  7. Chiu, J. J., L. J. Chen, P. L. Lee, C. I. Lee, L. W. Lo, et al. Shear stress inhibits adhesion molecule expression in vascular endothelial cells induced by coculture with smooth muscle cells. Blood 101:2667–2674, 2003.

    Article  CAS  PubMed  Google Scholar 

  8. Conway, E. M., D. Collen, and P. Carmeliet. Molecular mechanisms of blood vessel growth. Cardiovasc. Res. 49:507–521, 2001.

    Article  CAS  PubMed  Google Scholar 

  9. Conyers, G., L. Milks, M. Conklyn, and H. Showell. Cramer E.A factor in serum lowers resistance and opens tight junctions of MDCK cells. Am. J. Physiol. 259:C577–C585, 1990.

    CAS  PubMed  Google Scholar 

  10. Davies, P. F., G. A. Truskey, H. B. Warren, S. E. O’Connor, and B. H. Eisenhaure. Metabolic cooperation between vascular endothelial cells and smooth muscle cells in co-culture: changes in low density lipoprotein metabolism. J. Cell Biol. 101:871–879, 1985.

    Article  CAS  PubMed  Google Scholar 

  11. De Wit, C., M. Boettcher, and V. J. Schmidt. Signaling across myoendothelial gap junctions–fact or fiction? Cell Commun. Adhesion 15:231–245, 2008.

    Article  Google Scholar 

  12. DeMaio, L., J. M. Tarbell, R. C. Scaduto, Jr., T. W. Gardner, and D. A. Antonetti. A transmural pressure gradient induces mechanical and biological adaptive responses in endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 286:H731–H741, 2004.

    Article  CAS  PubMed  Google Scholar 

  13. Dora, K. A. Cell–cell communication in the vessel wall. Vasc. Med. 6:43–50, 2001.

    CAS  PubMed  Google Scholar 

  14. Dull, R. O., H. Jo, H. Sill, T. M. Hollis, and J. M. Tarbell. The effect of varying albumin concentration and hydrostatic pressure on hydraulic conductivity and albumin permeability of cultured endothelial monolayers. Microvasc. Res. 41:390–407, 1991.

    Article  CAS  PubMed  Google Scholar 

  15. Duthu, G. S., and J. R. Smith. In vitro proliferation and lifespan of bovine aorta endothelial cells: effect of culture conditions and fibroblast growth factor. J. Cell. Physiol. 103:385–392, 1980.

    Article  CAS  PubMed  Google Scholar 

  16. Fagotto, F., and B. M. Gumbiner. Cell contact-dependent signaling. Dev. Biol. 180:445–454, 1996.

    Article  CAS  PubMed  Google Scholar 

  17. Fillinger, M. F., L. N. Sampson, J. L. Cronenwett, R. J. Powell, and R. J. Wagner. Coculture of endothelial cells and smooth muscle cells in bilayer and conditioned media models. J. Surg. Res. 67:169–178, 1997.

    Article  CAS  PubMed  Google Scholar 

  18. Gaballa, M. A., T. E. Raya, B. R. Simon, and S. Goldman. Arterial mechanics in spontaneously hypertensive rats. Mechanical properties, hydraulic conductivity, and two-phase (solid/fluid) finite element models. Circ. Res. 71:145–158, 1992.

    Article  CAS  PubMed  Google Scholar 

  19. Gartner, L. P., and J. L. Hiatt. Circulatory system. In: Color Textbook of Histology, edited by B. Schmitt. Philadelphia: Saunders Co., 2001, pp. 251–256.

  20. Grazia Lampugnani, M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J. Cell Biol. 161:793–804, 2003.

    Article  PubMed  Google Scholar 

  21. Heberlein, K. R., A. C. Straub, and B. E. Isakson. The myoendothelial junction: breaking through the matrix? Microcirculation 16:307–322, 2009.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Heydarkhan-Hagvall, S., G. Helenius, B. R. Johansson, J. Y. Li, E. Mattsson, et al. Co-culture of endothelial cells and smooth muscle cells affects gene expression of angiogenic factors. J. Cell. Biochem. 89:1250–1259, 2003.

    Article  CAS  PubMed  Google Scholar 

  23. Hillsley, M. V., and J. M. Tarbell. Oscillatory shear alters endothelial hydraulic conductivity and nitric oxide levels. Biochem. Biophys. Res. Commun. 293:1466–1471, 2002.

    Article  CAS  PubMed  Google Scholar 

  24. Huang, Y., K. M. Jan, D. Rumschitzki, and S. Weinbaum. Structural changes in rat aortic intima due to transmural pressure. J. Biomech. Eng. 120:476–483, 1998.

    Article  CAS  PubMed  Google Scholar 

  25. Kurzen, H., S. Manns, G. Dandekar, T. Schmidt, S. Pratzel, et al. Tightening of endothelial cell contacts: a physiologic response to cocultures with smooth-muscle-like 10T1/2 cells. J. Investig. Dermatol. 119:143–153, 2002.

    Article  CAS  PubMed  Google Scholar 

  26. Langeler, E. G., and V. W. van Hinsbergh. Characterization of an in vitro model to study the permeability of human arterial endothelial cell monolayers. Thromb. Haemostasis 60:240–246, 1988.

    CAS  Google Scholar 

  27. Li, G., M. J. Simon, L. M. Cancel, Z. D. Shi, X. Ji, et al. Permeability of endothelial and astrocyte cocultures: in vitro blood–brain barrier models for drug delivery studies. Ann. Biomed. Eng. 38:2499–2511, 2010.

    Article  PubMed  Google Scholar 

  28. Mekata, F. Current spread in the smooth muscle of the rabbit aorta. J. Physiol. 242:143–155, 1974.

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Minnear, F. L., S. Patil, D. Bell, J. P. Gainor, and C. A. Morton. Platelet lipid(s) bound to albumin increases endothelial electrical resistance: mimicked by LPA. Am. J. Physiol. Lung Cell. Mol. Physiol. 281:L1337–L1344, 2001.

    CAS  PubMed  Google Scholar 

  30. Mortell, K. H., A. D. Marmorstein, and E. B. Cramer. Fetal bovine serum and other sera used in tissue culture increase epithelial permeability. In Vitro Cell. Dev. Biol. 29A:235–238, 1993.

    Article  CAS  PubMed  Google Scholar 

  31. Nitz, T., T. Eisenblätter, K. Psathaki, and H.-J. Galla. Serum-derived factors weaken the barrier properties of cultured porcine brain capillary endothelial cells in vitro. Brain Res. 981:30–40, 2003.

    Article  CAS  PubMed  Google Scholar 

  32. Pang, Z., and L. E. Niklason. Truskey. Porcine endothelial cells cocultured with smooth muscle cells became procoagulant in vitro. Tissue Eng. Part A 16:1835–1844, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Perez-Zoghbi, J. F., Y. Bai, and M. J. Sanderson. Nitric oxide induces airway smooth muscle cell relaxation by decreasing the frequency of agonist-induced Ca2+ oscillations. J. Gen. Physiol. 135:247–259, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Powers, M. R., F. A. Blumenstock, J. A. Cooper, and A. B. Malik. Role of albumin arginyl sites in albumin-induced reduction of endothelial hydraulic conductivity. J. Cell. Physiol. 141:558–564, 1989.

    Article  CAS  PubMed  Google Scholar 

  35. Qazi, H., R. Palomino, Z. D. Shi, and L. L. Munn. Tarbell JM. Integr. Biol. (Camb): Cancer cell glycocalyx mediates mechanotransduction and flow-regulated invasion, 2013.

    Google Scholar 

  36. Renkin, E. M., and F. E. Curry. Endothelial permeability: pathways and modulations. Ann. N. Y. Acad. Sci. 401:248–259, 1982.

    Article  CAS  PubMed  Google Scholar 

  37. Rose, S. L., and J. E. Babensee. Complimentary endothelial cell/smooth muscle cell co-culture systems with alternate smooth muscle cell phenotypes. Ann. Biomed. Eng. 35:1382–1390, 2007.

    Article  PubMed  Google Scholar 

  38. Ryan, U. S., J. W. Ryan, and C. Whitaker. How do kinins affect vascular tone? Adv. Exp. Med. Biol. 120A:375–391, 1979.

    Article  CAS  PubMed  Google Scholar 

  39. Schaper, W., and I. Buschmann. Arteriogenesis, the good and bad of it. Cardiovasc. Res. 43:835–837, 1999.

    Article  CAS  PubMed  Google Scholar 

  40. Shields, J. D., M. E. Fleury, C. Yong, A. A. Tomei, G. J. Randolph, et al. Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling. Cancer Cell 11:526–538, 2007.

    Article  CAS  PubMed  Google Scholar 

  41. Tada, S., and J. M. Tarbell. Interstitial flow through the internal elastic lamina affects shear stress on arterial smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 278:H1589–H1597, 2000.

    CAS  PubMed  Google Scholar 

  42. Tarbell, J. M. Shear stress and the endothelial transport barrier. Cardiovasc. Res. 87:320–330, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Tarbell, J. M., L. Demaio, and M. M. Zaw. Effect of pressure on hydraulic conductivity of endothelial monolayers: role of endothelial cleft shear stress. J. Appl. Physiol. 87:261–268, 1999.

    CAS  PubMed  Google Scholar 

  44. Tarbell, J. M., M. J. Lever, and C. G. Caro. The effect of varying albumin concentration of the hydraulic conductivity of the rabbit common carotid artery. Microvasc. Res. 35:204–220, 1988.

    Article  CAS  PubMed  Google Scholar 

  45. van Oostrom, M. C., O. van Oostrom, P. H. Quax, M. C. Verhaar, and I. E. Hoefer. Insights into mechanisms behind arteriogenesis: what does the future hold? J. Leukoc. Biol. 84:1379–1391, 2008.

    Article  PubMed  Google Scholar 

  46. Wen, H., Y. Lu, H. Yao, and S. Buch. Morphine induces expression of platelet-derived growth factor in human brain microvascular endothelial cells: implication for vascular permeability. PLoS One 6:e21707, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Ziegler, T., R. W. Alexander, and R. M. Nerem. An endothelial cell-smooth muscle cell co-culture model for use in the investigation of flow effects on vascular biology. Ann. Biomed. Eng. 23:216–225, 1995.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Heart, Lung, and Blood Institute Grant HL57093.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, City College of New York, New York, NY, USA

    Rishi A. Mathura, Sparkle Russell-Puleri, Limary M. Cancel & John M. Tarbell

Authors
  1. Rishi A. Mathura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sparkle Russell-Puleri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Limary M. Cancel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John M. Tarbell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John M. Tarbell.

Additional information

Associate Editor Peter E. McHugh oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mathura, R.A., Russell-Puleri, S., Cancel, L.M. et al. Hydraulic Conductivity of Endothelial Cell-Initiated Arterial Cocultures. Ann Biomed Eng 42, 763–775 (2014). https://doi.org/10.1007/s10439-013-0943-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-013-0943-y

Keywords

Search

Navigation