Abstract
Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited1,2. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferation and extracellular matrix deposition, followed later by superimposed atherosclerosis3. These changes directly compromise graft blood flow and provoke thrombosis. Vein graft wall thickening may represent an adaptation imposed by arterial hemodynamic factors4–6, and these factors have been shown to promote vascular smooth muscle cell migration and proliferation through activation of key mediators including platelet-derived growth factor (PDGF)7. Many pharmacological interventions aimed at preventing these long-term changes have proven unsuccessful in clinical evaluation8. We recently demonstrated in a pig saphenous vein graft model that application of an external polyester stent to the outside of carotid interposition vein grafts reduced intimal hyperplasia and total wall thickness 1 month after implantation9. However, it is not known whether the benefits of the stent are maintained in the longer term or what mechanisms underlie its effect. The present study therefore compared morphological changes and PDGF expression in stented grafts and contralateral unstented grafts in the same pigs, 6 months after graft implantation. Reduced medial thickening, neointima formation, and cell proliferation were sustained in externally stented grafts, and these effects were associated with a significant reduction in PDGF expression.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Campeau, L., et al. Atherosclerosis and late closure of saphenous vein grafts: Sequential angiographic studies 2 weeks, 1 year, 5 to 7 years and 10 to 12 years after surgery. Circulation 68 (Suppl. II), II.1–II.7 (1983).
Lytle, B., et al. Long term (5 to 12 years) serial studies of internal mammary artery and saphenous vein coronary bypass grafts. J. Thorac. Cardiovasc. Surg. 89, 248–258 (1985).
Angelini, G. & Newby, A. The future of saphenous vein as a coronary artery bypass conduit. Eur. Heart J. 10, 273–280 (1989).
Zwolak, R., Adams, M. & Clowes, A. Kinetics of vein graft hyperplasia: Association with tangential stress. J. Vase. Surg. 5, 126–136 (1987).
Morinaga, K., Okadome, K., Kuroki, M., Muto, Y. & Inokuchi, K. Effect of wall shear stress on intimal thickening of arterially transplanted autogenous veins in dogs. J. Vase. Surg. 2, 430–433 (1985).
Dobrin, P., Littooy, F. & Endean, E. Mechanical factors predisposing to intimal hyperplasia and medial thickening in autologous vein grafts. Surgery 105, 393–400 (1989).
Francis, S. et al. Release of platelet derived growth factor activity from arteriovenous bypass grafts. J. Thorac. Cardiovasc. Surg. 108, 540–548 (1994).
Bryan, A. & Angelini, G. The biology of saphenous vein graft occlusion: Etiology and strategies for prevention. Curr. Opin. Cardiol. 9, 641–649 (1994).
Angelini, G., Izzat, M. Bryan, A. & Newby, A. External stenting reduces wall thickening in arteriovenous bypass grafts. J. Thorac. Cardiovasc. Surg. 112, 79–84 (1996).
Angelini, G., et al. Time course of medial and intimal thickening in pig venous arterial grafts: Relationship to endothelial injury and cholesterol accumulation. J. Thorac. Cardiovasc. Surg. 103, 1093–1103 (1992).
Izzat, M., et al. The influence of external stent size on early medial and neointimal thickening in a pig model of saphenous vein bypass grafting. Circulation 94, 1741–1745 (1996).
Roussel, F. & Dalion, J. Lectins as markers of endothelial cells: Comparative study between human and animal cells. Lab Animal 22, 135–140 (1988).
George, S., Williams, A. & Newby, A. An essential role for platelet-derived growth factor in neointima formation in human saphenous vein in vitro. Atherosclerosis 120, 227–240 (1996).
Newby, A. & George, S. Proposed roles for growth factors in mediating smooth muscle proliferation in vascular pathologies. Cardiovasc. Res. 27, 1173–1183 (1993).
Ross, R., Raines, E. & Bowen-Pope, D. The biology of platelet-derived growth factor. Cell 46, 155–169 (1986).
Jawien, A., Bowen-Pope, D., Lindner, V., Schwartz, S. & Clowes, A. Platelet derived growth factor promotes smooth muscle cell migration and intimal thickening in a rat model of balloon angioplasty. J. Clin. Invest. 89, 507–511 (1992).
Nabel, E., et al. Recombinant platelet derived growth factor B gene expression in porcine arteries induces intimal hyperplasia in vivo. J. Clin. Invest 91, 1822–1829 (1993).
Ferns, C., et al. Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science 253, 1129–1132 (1991).
Francis, S., et al. Release of platelet derived growth factor activity from arteriovenous bypass grafts. J. Thorac. Cardiovasc. Surg. 108, 540–548 (1994).
Hoch, J.R., Stark, V.K., Hullett, D.A. & Turnipseed, W.D. Vein graft intimal hyperplasia - leukocytes and cytokine gene- expression. Surgery 116, 463–471 (1994).
Hoch, J.R., Stark, V.K. & Turnipseed, W.D. The temporal relationship between the development of vein graft intimal hyperplasia and growth-factor gene-expression. J. Vase. Surg 22, 51–58 (1995).
Barker, S., et al. The adventitia and atherogenesis: Removal initiates intimal proliferation in the rabbit which regresses on generation of a ‘neoadventitia’. Atherosclerosis 105, 131–144 (1994).
Barker, S., Talbert, A., Cottam, S., Baskerville, P. & Martin, J. Arterial intimal hyperplasia after occlusion of the adventitial vasa vasorum in the pig. Arterioscler. Thromb. 13, 70–77 (1993).
Goldman, S., et al. Long term graft patency (3 years) after coronary artery surgery: Effects of aspirin. Results of a VA Cooperative Study. Circulation 89, 1138–1143 (1994).
Zilla, P., von Oppell, U. & Deutsch, M. The endothelium: A key to the future. J. Cardiac Surg. 8, 32–60 (1993).
Kohler, T., Kirkman, T. & Clowes, A. The effect of rigid external support on vein graft adaptation to the arterial circulation. J. Vase. Surg. 9, 277–285 (1989).
Violaris, A., Newby, A. & Angelini, G. Effects of external stenting on wall thickening in arteriovenous bypass grafts. Ann. Thorac. Surg. 55, 667–671 (1993).
Karayannacos, P. et al. Late failure in vein grafts: Mediating factors in subendothelial fibromuscular hyperplasia. Ann. Surg. 187, 183–188 (1978).
Home Office Animals (Scientific Procedures) Act 1986. Guidance on the operation on animals. (HMSO, London, 1990).
Galand, P. & Degraef, C. Cyclin/PCNA immunostaining as an alternative to tritiated thymidine pulse labelling for marking S-phase cells in paraffin sections from animal and human tissues. Cell Tissue Kinet. 22, 383–392 (1989).
Soyombo, A., Angelini, G., Bryan, A., Jasani, B. & Newby, A. Intimal proliferation in an organ culture of human saphenous vein. Am. J. Pathol. 137, 1401–1410 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mehta, D., George, S., Jeremy, J. et al. External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting. Nat Med 4, 235–239 (1998). https://doi.org/10.1038/nm0298-235
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nm0298-235
This article is cited by
-
Vasa vasorum inside out/outside in communication: a potential role in the patency of saphenous vein coronary artery bypass grafts
Journal of Cell Communication and Signaling (2018)
-
Dysregulation of angiogenesis-specific signalling in adult testis results in xenograft degeneration
Scientific Reports (2017)
-
A novel biodegradable external mesh stent improved long-term patency of vein grafts by inhibiting intimal–medial hyperplasia in an experimental canine model
General Thoracic and Cardiovascular Surgery (2016)
-
Expandable external support device to improve Saphenous Vein Graft Patency after CABG
Journal of Cardiothoracic Surgery (2013)
-
Vein graft failure: current clinical practice and potential for gene therapeutics
Gene Therapy (2012)