Novel Approach for Endothelializing Vascular Devices: Understanding and Exploiting Elastin–Endothelial Interactions
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Elastin is an essential component of arteries which provides structural integrity and instructs smooth muscle cells to adopt a quiescent state. Despite interaction of endothelial cells with elastin in the internal elastic lamina, the potential for exploiting this interaction therapeutically has not been explored in detail. In this study, we show that tropoelastin (a precursor of elastin) stimulates endothelial cell migration and adhesion more than smooth muscle cells. The biological activity of tropoelastin on endothelial cells is contained in the VGVAPG domain and in the carboxy-terminal 17-amino acids. We show that the effects of the carboxy-terminal 17 amino acids, but not those of VGVAPG, are mediated by integrin αVβ3. We demonstrate that tropoelastin covalently linked to stainless steel disks promotes adhesion of endothelial progenitor cells and endothelial cells to the metal surfaces. The adherent cells on the tropoelastin-coated metal surfaces form monolayers that can withstand and respond to arterial shear stress. Because of the unique effects of tropoelastin on endothelial and smooth muscle cells, coating intravascular devices with tropoelastin may stimulate their endothelialization, inhibit smooth muscle hyperplasia, and improve device performance.
- Aoki, J., P. W. Serruys, H. van Beusekom, A. T. Ong, E. P. McFadden, G. Sianos, W. J. van der Giessen, E. Regar, P. J. de Feyter, H. R. Davis, S. Rowland, and M. J. Kutryk. Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry. J. Am. Coll. Cardiol. 45:1574–1579, 2005. CrossRef
- Asai, J., H. Takenaka, K. F. Kusano, M. Ii, C. Luedemann, C. Curry, E. Eaton, A. Iwakura, Y. Tsutsumi, H. Hamada, S. Kishimoto, T. Thorne, R. Kishore, and D. W. Losordo. Topical sonic hedgehog gene therapy accelerates wound healing in diabetes by enhancing endothelial progenitor cell-mediated microvascular remodeling. Circulation 113:2413–2424, 2006. CrossRef
- Aznavoorian, S., M. L. Stracke, J. Parsons, J. McClanahan, and L. A. Liotta. Integrin alphavbeta3 mediates chemotactic and haptotactic motility in human melanoma cells through different signaling pathways. J. Biol. Chem. 271:3247–3254, 1996. CrossRef
- Bax, D. V., U. R. Rodgers, M. M. Bilek, and A. S. Weiss. Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3. J. Biol. Chem. 284:2816–2823, 2009. CrossRef
- Blood, C. H., J. Sasse, P. Brodt, and B. R. Zetter. Identification of a tumor cell receptor for VGVAPG, an elastin-derived chemotactic peptide. J. Cell. Biol. 107:1987–1993, 1988. CrossRef
- Bose, D., F. Meric-Bernstam, W. Hofstetter, D. A. Reardon, K. T. Flaherty, and L. M. Ellis. Vascular endothelial growth factor targeted therapy in the perioperative setting: implications for patient care. Lancet Oncol. 11:373–382, 2010. CrossRef
- Broekelmann, T. J., B. A. Kozel, H. Ishibashi, C. C. Werneck, F. W. Keeley, L. Zhang, and R. P. Mecham. Tropoelastin interacts with cell-surface glycosaminoglycans via its COOH-terminal domain. J. Biol. Chem. 280:40939–40947, 2005. CrossRef
- Cheresh, D. A., and R. C. Spiro. Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J. Biol. Chem. 262:17703–17711, 1987.
- Conway, E. M., D. Collen, and P. Carmeliet. Molecular mechanisms of blood vessel growth. Cardiovasc. Res. 49:507–521, 2001. CrossRef
- Daamen, W. F., J. H. Veerkamp, J. C. van Hest, and T. H. van Kuppevelt. Elastin as a biomaterial for tissue engineering. Biomaterials 28:4378–4398, 2007. CrossRef
- Frangos, J. A., S. G. Eskin, L. V. McIntire, and C. L. Ives. Flow effects on prostacyclin production by cultured human endothelial cells. Science 227:1477–1479, 1985. CrossRef
- Gallant, N. D., and A. J. Garcia. Quantitative analyses of cell adhesion strength. Methods Mol. Biol. 370:83–96, 2007. CrossRef
- Girard, P. R., and R. M. Nerem. Shear stress modulates endothelial cell morphology and F-actin organization through the regulation of focal adhesion-associated proteins. J. Cell. Physiol. 163:179–193, 1995. CrossRef
- Hedman, M., J. Hartikainen, M. Syvanne, J. Stjernvall, A. Hedman, A. Kivela, E. Vanninen, H. Mussalo, E. Kauppila, S. Simula, O. Narvanen, A. Rantala, K. Peuhkurinen, M. S. Nieminen, M. Laakso, and S. Yla-Herttuala. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation 107:2677–2683, 2003. CrossRef
- Hinek, A., D. S. Wrenn, R. P. Mecham, and S. H. Barondes. The elastin receptor: a galactoside-binding protein. Science 239:1539–1541, 1988. CrossRef
- Hornebeck, W., J. M. Tixier, and L. Robert. Inducible adhesion of mesenchymal cells to elastic fibers: elastonectin. Proc. Natl Acad. Sci. USA 83:5517–5520, 1986. CrossRef
- Ii, M., H. Nishimura, A. Iwakura, A. Wecker, E. Eaton, T. Asahara, and D. W. Losordo. Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via “imported” nitric oxide synthase activity. Circulation 111:1114–1120, 2005. CrossRef
- Ito, S., S. Ishimaru, and S. E. Wilson. Application of coacervated alpha-elastin to arterial prostheses for inhibition of anastomotic intimal hyperplasia. ASAIO J. 44:M501–M505, 1998. CrossRef
- Ito, S., S. Ishimaru, and S. E. Wilson. Effect of coacervated alpha-elastin on proliferation of vascular smooth muscle and endothelial cells. Angiology 49:289–297, 1998. CrossRef
- Karnik, S. K., B. S. Brooke, A. Bayes-Genis, L. Sorensen, J. D. Wythe, R. S. Schwartz, M. T. Keating, and D. Y. Li. A critical role for elastin signaling in vascular morphogenesis and disease. Development 130:411–423, 2003. CrossRef
- Karnik, S. K., J. D. Wythe, L. Sorensen, B. S. Brooke, L. D. Urness, and D. Y. Li. Elastin induces myofibrillogenesis via a specific domain, VGVAPG. Matrix Biol. 22:409–425, 2003. CrossRef
- Kikkawa, Y., N. Sanzen, H. Fujiwara, A. Sonnenberg, and K. Sekiguchi. Integrin binding specificity of laminin-10/11: laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrins. J. Cell Sci. 113(Pt 5):869–876, 2000.
- Kipshidze, N., G. Dangas, M. Tsapenko, J. Moses, M. B. Leon, M. Kutryk, and P. Serruys. Role of the endothelium in modulating neointimal formation: vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions. J. Am. Coll. Cardiol. 44:733–739, 2004.
- Klomp, M., M. A. Beijk, and R. J. de Winter. Genous endothelial progenitor cell-capturing stent system: a novel stent technology. Expert Rev. Med. Dev. 6:365–375, 2009. CrossRef
- McFadden, E. P., E. Stabile, E. Regar, E. Cheneau, A. T. Ong, T. Kinnaird, W. O. Suddath, N. J. Weissman, R. Torguson, K. M. Kent, A. D. Pichard, L. F. Satler, R. Waksman, and P. W. Serruys. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 364:1519–1521, 2004. CrossRef
- Mejia, J., B. Ruzzeh, R. Mongrain, R. Leask, and O. F. Bertrand. Evaluation of the effect of stent strut profile on shear stress distribution using statistical moments. Biomed. Eng. Online 8:8, 2009. CrossRef
- Nonaka, R., S. Onoue, H. Wachi, F. Sato, Z. Urban, B. C. Starcher, and Y. Seyama. DANCE/fibulin-5 promotes elastic fiber formation in a tropoelastin isoform-dependent manner. Clin. Biochem. 42:713–721, 2009. CrossRef
- Park, C. C., J. C. Morel, M. A. Amin, M. A. Connors, L. A. Harlow, and A. E. Koch. Evidence of IL-18 as a novel angiogenic mediator. J. Immunol. 167:1644–1653, 2001.
- Plow, E. F., T. A. Haas, L. Zhang, J. Loftus, and J. W. Smith. Ligand binding to integrins. J. Biol. Chem. 275:21785–21788, 2000. CrossRef
- Ramirez, F., and H. C. Dietz. Extracellular microfibrils in vertebrate development and disease processes. J. Biol. Chem. 284:14677–14681, 2009. CrossRef
- Rodgers, U. R., and A. S. Weiss. Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin. Biochimie 86:173–178, 2004. CrossRef
- Rosenbloom, J., W. R. Abrams, and R. Mecham. Extracellular matrix 4: the elastic fiber. FASEB J. 7:1208–1218, 1993.
- Shiu, Y. T., S. Li, W. A. Marganski, S. Usami, M. A. Schwartz, Y. L. Wang, M. Dembo, and S. Chien. Rho mediates the shear-enhancement of endothelial cell migration and traction force generation. Biophys. J. 86:2558–2565, 2004. CrossRef
- Spencer, J. A., S. L. Hacker, E. C. Davis, R. P. Mecham, R. H. Knutsen, D. Y. Li, R. D. Gerard, J. A. Richardson, E. N. Olson, and H. Yanagisawa. Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration. Proc. Natl Acad. Sci. USA 102:2946–2951, 2005. CrossRef
- Stracke, M. L., J. D. Engel, L. W. Wilson, M. M. Rechler, L. A. Liotta, and E. Schiffmann. The type I insulin-like growth factor receptor is a motility receptor in human melanoma cells. J. Biol. Chem. 264:21544–21549, 1989.
- Sutherland, D. R., L. Anderson, M. Keeney, R. Nayar, and I. Chin-Yee. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J. Hematother. 5:213–226, 1996.
- Swanson, N., K. Hogrefe, Q. Javed, N. Malik, and A. H. Gershlick. Vascular endothelial growth factor (VEGF)-eluting stents: in vivo effects on thrombosis, endothelialization and intimal hyperplasia. J. Invasive Cardiol. 15:688–692, 2003.
- Tzima, E., M. A. del Pozo, S. J. Shattil, S. Chien, and M. A. Schwartz. Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. EMBO J. 20:4639–4647, 2001. CrossRef
- Wachi, H., R. Nonaka, F. Sato, K. Shibata-Sato, M. Ishida, S. Iketani, I. Maeda, K. Okamoto, Z. Urban, S. Onoue, and Y. Seyama. Characterization of the molecular interaction between tropoelastin and DANCE/fibulin-5. J. Biochem. 143:633–639, 2008. CrossRef
- Williamson, M. R., A. Shuttleworth, A. E. Canfield, R. A. Black, and C. M. Kielty. The role of endothelial cell attachment to elastic fibre molecules in the enhancement of monolayer formation and retention, and the inhibition of smooth muscle cell recruitment. Biomaterials 28:5307–5318, 2007. CrossRef
- Yin, Y., S. G. Wise, N. J. Nosworthy, A. Waterhouse, D. V. Bax, H. Youssef, M. J. Byrom, M. M. Bilek, D. R. McKenzie, A. S. Weiss, and M. K. Ng. Covalent immobilisation of tropoelastin on a plasma deposited interface for enhancement of endothelialisation on metal surfaces. Biomaterials 30:1675–1681, 2009. CrossRef
- Yoshigi, M., E. B. Clark, and H. J. Yost. Quantification of stretch-induced cytoskeletal remodeling in vascular endothelial cells by image processing. Cytometry A 55:109–118, 2003. CrossRef
- Novel Approach for Endothelializing Vascular Devices: Understanding and Exploiting Elastin–Endothelial Interactions
Annals of Biomedical Engineering
Volume 39, Issue 1 , pp 337-346
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Division of Cardiology, University of Utah, Salt Lake City, UT, 84112, USA
- 2. Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84112, USA
- 3. Program in Molecular Medicine, University of Utah, Salt Lake City, UT, 84112, USA
- 4. Department of Bioengineering, University of Utah, Salt Lake City, UT, 84112, USA
- 6. OrbusNeich Medical, Incorporated, Fort Lauderdale, FL, 33309, USA
- 5. Division of Hematology, University of Utah, Salt Lake City, UT, 84112, USA
- 7. Eccles Institute of Human Genetics, University of Utah, Room 4450, 15 North 2030 East, Salt Lake City, UT, 84112, USA