Abstract
Substantial progress has been made in our understanding of the genetic causes of human diseases. Advances in genomic research has resulted in the identification of many disease causing genes and their chromosomal localization. Along with discoveries in human genetics has been the development of methods to treat human diseases with recombinant DNA, that is, human gene therapy. While this field is still in its infancy, several principles have been established. Recombinant genes can be introduced into human somatic cells in vivo where their expression and function can be detected and quantified. Major challenges exist to refine delivery methods and vectors in order to increase expression within cells and minimize possible toxicity of vectors to the host. In addition, it is likely that genetic treatments will be used in many diseases, and the challenge to physicians is to determine “which genes for which diseases.” In this chapter, we will review the prospects for using gene therapy to treat coronary artery restenosis and other vascular diseases characterized by abnormalities in cell proliferation. In addition, we will discuss the role of gene therapy for the vascular remodeling process.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801–809.
Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995;91:2844–2850.
Lafont A, Guzman LA, Whitlow PL, Goormastic M, Comhill JF, Chisolm GM. Restenosis after experimental angioplasty. Intimai, medial, and adventitial changes associated with constrictive remodeling. Circ Res 1995;76:996–1002.
Nabel E.G., Yang Z, Liptay S, San H, Gordon D, Haudenschild CC, Nabel GJ. Recombinant platelet-derived growth factor B gene expression in porcine arteries induces intimai hyperplasia in vivo. J Clin Invest 1993;91:1822–1829.
Pompili VJ, Gordon D, San H, Yang ZY, Muller DWM, Nabel GJ, Nabel EG. Expression and function of a recombinant PDGF B gene in porcine arteries. Arterioscler Thromb Vasc Biol 1995;15:2254–2264.
Nabel EG, Yang Z, Plautz G, Forough R, Zhan X, Haudenschild CC, Maciag T, and Nabel GJ. Recombinant fibroblast growth factor-1 promotes intimai hyperplasia and angiogenesis in arteries in vivo. Nature 1993;362:844–846.
Nabel EG, Shum L, Pompili V1, Yang Z, San H, Shu HB, Liptay S, Gold L, Gordon D, Derynck R, Nabel GJ. Direct transfer of transforming growth factor bl gene into arteries stimulates fibrocellular hyperplasia. Proc Natl Acad Sci USA 1993;90:10759–10763.
Ohno T, Gordon D, San H, Pompili VJ, Imperiale VJ, Nabel GJ, Nabel EG. Gene therapy for vascular smooth muscle cell proliferation after arterial injury. Science 1994;265:781–784.
Guzman RJ, Hirschowitz EA, Brody SL, Crystal RG, Epstein SE, Finkel T. In vivo suppression of injury-induced vascular smooth muscle cell accumulation using adenovirus-mediated transfer of herpes simplex thymidine kinase gene. Proc Natl Acad Sci USA 1994;91:10732–10736.
Chang MW, Ohno T, Gordon D, Lu MM, Nabel GJ, Nabel EG, Leiden JM. Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene inhibits vascular smooth muscle cell proliferation and neointima formation following balloon angioplasty of the rat carotid artery. Mol Med 1995;1:172–181.
Simari R, San H, Rekhter M, Ohno T, Gordon D, Nabel EG. Regulation of cellular proliferation and intimai formation following balloon injury in atherosclerotic rabbit arteries. J Clin Invest 1996;98:225–235.
Peter M, Herskowitz I. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle. Cell 1994;79:181–184.
Shen CJ, Roberts JM. 1995. Inhibitors of mammalian GI cyclin-dependent kinases. Genes Dev 1995;9:1149–1163.
Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature 1993;366:701–704
Yang Z, Simari R, Perkins N, San H, Gordon D, Nabel GJ, Nabel EG. 1996. Role of the p21 cyclindependent kinase inhibitor in limiting intimai cell proliferation in response to arterial injury. Proc Natl Acad Sci USA 1996;93:7905–7910.
Chang MW, Barr E, Lu M, Barton K, Leiden JM. 1995. 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 1995;96:2260–2268.
Tahil O, Branellec D, Aubailly N, Ddieu JF, LeFeuvre C, Ratet N, Caillaud JM, Barry JJ, Perricaudet M, Feldman LJ, Denefle P, Steg PG. Reduction of restenosis after angioplasty by gene therapy with HSV-tk and ganciclovir. Results from a double injury model in the hypercholesterolemic rabbit. Circulation 1995;92:I-295.
Chang MW, Barr E, Seltzer J, Jian YQ, Nabel GJ, Nabel EG, Parmacek MS, Leiden JM. Cytostatic gene therapy for vascular proliferative disorders using a constitutively active form of Rb. Science 1995;267:518–522.
Yang Z, Simari RD, Tanner F, Stephen D, Nabel GJ, Nabel EG. Gene transfer approaches to the regulation of vascular cell proliferation. Semin Intervent Cardiol 1996;in press.
Libby P, Swanson SJ, Tanaka H, Murray A, Schoen FJ, Pober JS. Immunopathology of coronary arteriosclerosis in transplanted hearts. J Heart Lung Transplant 1992;11:S5–S6.
Cowan B, Baron O, Crack J, Coulber C, Wilson GJ, Rabinovitch M. Elafin, a serine elastase inhibitor, attenuates post-cardiac transplant coronary arteriopathy and reduces myocardial necrosis in rabbits after heterotopic cardiac translantation. J Clin Invest 1996;97:2452–2468.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media New York
About this chapter
Cite this chapter
Tanner, F., Yang, Z., Simari, R.D., Nabel, E.G. (1997). Gene Transfer and Vascular Remodeling. In: Lafont, A., Topol, E.J. (eds) Arterial Remodeling: A Critical Factor in Restenosis. Developments in Cardiovascular Medicine, vol 198. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6079-1_27
Download citation
DOI: https://doi.org/10.1007/978-1-4615-6079-1_27
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7785-6
Online ISBN: 978-1-4615-6079-1
eBook Packages: Springer Book Archive