Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Vascular Remodeling and Lesion Formation in Restenosis: Implications for Nitric Oxide-Based Therapeutics

  • Chapter
Arterial Remodeling: A Critical Factor in Restenosis

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 198))

  • 67 Accesses

Abstract

The problem of restenosis after angioplasty procedures is one of the most vexing clinical issues in cardiovascular medicine. Although advances in device technology have been significant, the utility of interventional strategies such as stents is still compromised by restenosis. It is hoped that the development of more effective therapeutic strategies to prevent restenosis will be facilitated by an insightful understanding of the underlying pathobiological mechanisms that cause restenosis. This brief review will discuss emerging concepts on the etiology of restenosis and the development of novel therapeutic strategies. In particular, it will focus on the potential role of nitric oxide as a critical determinant of vascular remodeling and lesion formation as well as nitric oxide-based therapies as a treatment strategy to prevent restenosis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Lehmann KG, Melkert R, Serruys PW. Contributions of frequency distribution analysis to the understanding of coronary restenosis. A reappraisal of the gaussian curve. Circulation 1996 93(6):1123–32.

    Article  PubMed  CAS  Google Scholar 

  2. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993 362(6423):801–9.

    Article  PubMed  CAS  Google Scholar 

  3. Mintz GS, Popma JJ, Hong MK, Pichard AD, Kent KM, Satler L, Leon MB. Intravascular ultrasound to discern device-specific effects and mechanisms of restenosis. Am J Cardiol 1996 78(3A):18–22.

    Article  PubMed  CAS  Google Scholar 

  4. Gibbons GH, Dzau VJ: The emerging concept of vascular remodeling. New Engl J Medicine 1994;330:1431–1438.

    Article  CAS  Google Scholar 

  5. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh A. Failure of blood-island formation and vasculogenesis in Flk-1 deficient mice. Nature 1995 376(6535):62–6.

    Article  PubMed  CAS  Google Scholar 

  6. Risau W, Flamme L. Vasculogenesis. Ann Rev Cell Dev Biol 1995 11:73–91.

    Article  CAS  Google Scholar 

  7. Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, Gridley T, Wolburg H, Risau W, Qin Y. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 1995 376(6535):70–4.

    Article  PubMed  CAS  Google Scholar 

  8. Langille BL, O’Donnell F. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 1986;231(4736):405–7.

    Article  PubMed  CAS  Google Scholar 

  9. Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev 1995; 75(3):519–60.

    PubMed  CAS  Google Scholar 

  10. Ohno M, Cooke JP, Gibbons GH: Fluid shear stress induces endothelial TGFb1 transcription and production: modulation by flow-activated potassium channels. J Clin Invest 1995; 95:1363–1369.

    Article  PubMed  CAS  Google Scholar 

  11. Kamiya A., Togawa T. Adaptive regulation of wall shear stress to flow change in the canine carotid artery. Am. J. Physiol. 1980; 239:H14–H21.

    PubMed  CAS  Google Scholar 

  12. Glagov, S., Weisenberg, E. Zarins, C.K., Stankunavicius, R., Kolettis, G.J. Compensatory enlargement of human atherosclerotic coronary arteries. N. Engl. J. Med. 1987; 316:1371–1375.

    Article  PubMed  CAS  Google Scholar 

  13. Steinke W, Els T, Hennerici M. Compensatory carotid artery dilatation in early atherosclerosis. Circulation 1994; 89:2578–2581.

    Article  PubMed  CAS  Google Scholar 

  14. Ohno M, Gibbons GH, Dzau VJ, Cooke JP: Shear stress elevates endothelial cGMP: Role of a potassium channel and G-protein coupling. Circulation 1993 88:193–197.

    Article  PubMed  CAS  Google Scholar 

  15. Uematsu M, Ohara Y, Navas JP, Nishida K, Murphy TJ, Alexander RW, Nerem RM, Harrison DG. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 1995; 269:C1371–8.

    PubMed  CAS  Google Scholar 

  16. Miller VM, Burnett JC Jr. Modulation of NO and endothelin by chronic increases in blood flow in canine femoral arteries. Am J Physiol 1992; 263:H103–8.

    PubMed  CAS  Google Scholar 

  17. Tronc F, Wassef M, Esposito B, Henrion D, Glagov S, Tedgui A. Role of NO in flow-induced remodeling of the rabbit common carotid artery. Arterioscler Throm Vasc Biol 1996; 16:1256–1262.

    Article  CAS  Google Scholar 

  18. Kramsch DM, Aspen M, Abramowitz BM, Kreimendahl T, Hood WB. Reduction of coronary atherosclerosis by moderate conditioning exercise in monkeys on an atherogenic diet. N Engl J Med 1981;305:1483–1489.

    Article  PubMed  CAS  Google Scholar 

  19. Haskell WL, Sims C, Myll J, Bortz WM, St Goar FG, Alderman EL. Coronary artery size and dilating capacity in ultradistance runners. Circulation 1993; 87:1076–82.

    Article  PubMed  CAS  Google Scholar 

  20. Sinoway LI, Shenberger J, Wilson J, McLaughlin D, Musch T, Zelis R. A 30-day forearm work protocol increases maximal forearm blood flow. J. Appl Physiol 1987; 62(3):1063–7.

    PubMed  CAS  Google Scholar 

  21. Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 1994; 74(2):349–53.

    Article  PubMed  CAS  Google Scholar 

  22. Maroun MJ, Mehta S, Turcotte R, Cosio MG, Hussain SN. Effects of physical conditioning on endogenous nitric oxide output during exercise. J Appl Physiol 1995; 79(4):1219–25.

    PubMed  CAS  Google Scholar 

  23. Malek AM, Gibbons GH, Dzau VJ, Izumo S: Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B-chain in vascular endothelium. J Clin Invest 1993; 92: 2013–21.

    Article  PubMed  CAS  Google Scholar 

  24. Cho A; Courtman DW; Langille BL.Apoptosis (programmed cell death) in arteries of the neonatal lamb. Circ Res, 1995; 76:168–175.

    Article  PubMed  CAS  Google Scholar 

  25. Kondo S, Y Dali, Aoki T, Takahashi JA, Morimura T, Takeuchi J. Bc1–2 gene prevents apoptosis of basic fibroblast growth factor-deprived murine aortic endothelial cells. Exp Cell Res 1994; 213:428–432.

    Article  PubMed  CAS  Google Scholar 

  26. Dimmeler S, Haendeler J, Neuls M, Zeiher AM. Shear stress prevents apoptosis of human endothelial cells. Circulation 1996; 94:I-471 (abstract).

    Google Scholar 

  27. Haendeler J, Dimmeler S, Nenis M, Zeiher AM. Nitric oxide inhibits TNF induced apoptosis of human endothelial cells: role of interleukin-)beta converting enzyme-like proteases. Circulation 1996; 94:1–155 (abstract).

    Article  Google Scholar 

  28. Moroi M, Gold HK, Yasuda T, Fishman MC, Huang PL. Mice mutant in endothelial nitric oxide synthase: vessel growth and response to injury. Circulation 1996; 94:1–154 (abstract).

    Article  Google Scholar 

  29. Reidy MA, Clowes AW, Schwartz SM. Endothelial regeneration. V. Inhibition of endothelial regrowth in arteries of rat and rabbit. Lab Invest 1983; 49(5):569–75.

    PubMed  CAS  Google Scholar 

  30. Bjomsson TD, Dryjski M, Tluczek J, Mennie R, Ronan J, Mellin TN, Thomas KA. Acidic fibroblast growth factor promotes vascular repair. Proc Nati Acad Sci U S A 1991; 88(19):8651–5.

    Article  Google Scholar 

  31. Nathan A, Nugent MA, Edelman ER. Tissue engineered perivascular endothelial cell implants regulate vascular Proc Natl Acad Sci USA 1995; 92(18):8130–4.

    Article  PubMed  CAS  Google Scholar 

  32. Faulkner, S.L., Fisher, R.D., Conkle, D.M., Page, D.L., Bender, H.W. Effect of blood flow rate on subendothelial proliferation in venous autografts used as arterial substitutes. Circulation 1975; 51/52 (Suppl 1):I-163–I-172.

    Google Scholar 

  33. Kraiss, L.W., Kirkman, T.R., Kohler, T.R., Zierler, B., Clowes, A.W. Shear stress regulates smooth muscle proliferation and neointimal thickening in porous polytetrapluroethylene grafts. Arteriosclerosis and Thrombosis 1991; 11:1844–1852.

    Article  PubMed  CAS  Google Scholar 

  34. Geary RL; Kohler TR; Vergel S; Kirkman TR; Clowes AW. Time course of flow-induced smooth muscle cell proliferation and intimal thickening in endothelialized baboon vascular grafts. Circ Res 1994; 74:14–23.

    Article  PubMed  CAS  Google Scholar 

  35. Ellenby MI, Ernst CB, Carretero OA, Scicli AG. Role of nitric oxide in the effect of blood flow on neointima formation. J Vasc Surg 1996; 23(2):314–22.

    Article  PubMed  CAS  Google Scholar 

  36. Bendeck MP; Zempo N; Clowes AW; Galardy RE; Reidy MA. Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat. Circ Res, 1994; 75:539–45.

    Article  PubMed  CAS  Google Scholar 

  37. Trachtman H, Futterweit S, Garg P, Reddy K, Singhal PC. Nitric oxide stimulates the activity of a 72kDa neutral matrix metalloproteinase in cultured rat mesangial cells. Biochem Biophys Res Commun 1996; 218(3):704–8.

    Article  PubMed  CAS  Google Scholar 

  38. Trachtman H, Futterweit S, Singhal P. Nitric oxide modulates the synthesis of extracellular matrix proteins in cultured rat mesangial cells/ Biochem Biophys Res Commun 1995; 207(1):120–5.

    Article  PubMed  CAS  Google Scholar 

  39. Wong LC, Langille BL. Developmental remodeling of the internal elastic lamina of rabbit arteries: effect of blood flow. Cire Res 1996; 78(5):799–805

    Article  CAS  Google Scholar 

  40. Ashizawa N, Graf K, Do YS, Nunohiro T, Giachelli CM, Meehan WP, Tuan TL, Hsueh WA.Osteopontin Is Produced by Rat Cardiac Fibroblasts and Mediates All-induced DNA Synthesis and Collagen Gel Contraction. J. Clin. Invest. 1996 98: 2218–2227.

    Article  PubMed  CAS  Google Scholar 

  41. Hou J, Kato H, Cohen RA, Chobanian AV, Brecher P. Angiotensin II-induced cardiac fibrosis in the rat is increased by chronic inhibition of nitric oxide synthase. J Clin Invest 1995; 96(5):2469–77.

    Article  PubMed  CAS  Google Scholar 

  42. Radomski MW, Moncada S. The biological and pharmacological role of nitric oxide in platelet function. Adv Exp Med Biol 1993; 344:251–64.

    Article  PubMed  CAS  Google Scholar 

  43. Yao SK, Akhtar S, Scott-Burden T, Ober JC, Golino P, Buja LM, Casscells W, Willerson JT, Endogenous and exogenous nitric oxide protect against intracoronary thrombosis and reocclusion after thrombolysis. Circulation 1995;92(4):1005–10.

    Article  PubMed  CAS  Google Scholar 

  44. von der Leyen H, Gibbons GH, Morishita R, Lewis NP, Zhang L, Kaneda Y, Cooke JP, Dzau VJ. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci USA 1995;92: 1137–1141.

    Article  PubMed  Google Scholar 

  45. Dubey RK, Jackson EK, Luscher TF. Nitric oxide inhibits angiotensin II-induced migration of rat aortic smooth muscle cell. Role of cyclic-nucleotides and angiotensin 1 receptors. J Clin Invest 1995;96(1):141–9.

    Article  PubMed  CAS  Google Scholar 

  46. Pauly RR, Bilato C, Sollott SJ, Monticone R, Kelly PT, Lakatta EG, Crow MT. Role of calcium/calmodulin-dependent protein kinase II in the regulation of vascular smooth muscle cell migration. Circulation 1995; 91(4):1107–15.

    Article  PubMed  CAS  Google Scholar 

  47. Ziche M, Morbidelli L, Masini E, Amerini S, Granger HJ, Maggi CA, Geppetti P, Ledda F. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest 1994;94(5):2036–44.

    Article  PubMed  CAS  Google Scholar 

  48. Guo JP, Panday MM, Consigny PM, Lefer AM. Mechanisms of vascular preservation by a novel NO donor following rat carotid artery intimal injury. Am J Physiol 1995;269(3 Pt 2):H1122–31.

    PubMed  CAS  Google Scholar 

  49. Scott NA, Cipolla GD, Ross CE, Dunn B, Martin FH, Simonet L, Wilcox JN. Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries. Circulation 1996;93(12):2178–87 1996.

    Article  CAS  Google Scholar 

  50. Shah PK, Falk E, Badimon JJ, Femandez-Ortiz A, Mailhac A, Villareal-Levy G, Fallon JT, Regnstrom J, Fuster V. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 1995; 92(6):1565–9.

    PubMed  CAS  Google Scholar 

  51. Cayatte AJ, Palacino JJ, Horten K, Cohen RA. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb 1994;14(5):753–9.

    Article  PubMed  CAS  Google Scholar 

  52. Tsao PS, McEvoy LM, Drexler H, Butcher EC, Cooke JP. Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine. Circulation 1994;89(5):2176–82.

    Article  PubMed  CAS  Google Scholar 

  53. De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MA Jr, Shin WS, Liao JK. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 1995 96(1):60–8.

    Article  PubMed  Google Scholar 

  54. Tsao PS, Lewis NP, Alpert S, Cooke JP. Exposure to shear stress alters endothelial adhesiveness. Role of nitric oxide. Circulation 1995;92(12):3513–9.

    Article  PubMed  CAS  Google Scholar 

  55. Peng HB, Libby P, Liao JK. Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B. J Biol Chem 1995;270(23):14214–9.

    Article  PubMed  CAS  Google Scholar 

  56. Garg, UC, Hassid, A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J. Clin. Irwest.1989;83:1774–1777.

    Article  CAS  Google Scholar 

  57. Tarry WC, Makhoul RG. L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty. Arterioscler Thromb 1994;14(6):938–43.

    Article  PubMed  CAS  Google Scholar 

  58. Marks DS, Vita JA, Folts JD, Keaney JF Jr, Welch GN, Loscalzo J. Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide. J Clin Invest 1995;96(6):2630–8.

    Article  PubMed  CAS  Google Scholar 

  59. De Meyer GR, Bult H, Ustunes L, Kockx MM, Feelisch M, Herman AG. Effect of nitric oxide donors on neointima formation and vascular reactivity in the collared carotid artery of rabbits. J Cardiovasc Pharrracol 1995;26(2):272–9.

    Article  Google Scholar 

  60. Groves PH, Banning AP, Penny WJ, Newby AC, Cheadle HA, Lewis MJ. The effects of exogenous nitric oxide on smooth muscle cell proliferation following porcine carotid angioplasty. Cardiovasc Res 1995;30(1):87–96.

    PubMed  CAS  Google Scholar 

  61. Isner JM, Kearney M, Bortman S, Passeri J. Apoptosis in human atherosclerosis and restenosis. Circulation 1995;91(II):2703–11.

    Article  PubMed  CAS  Google Scholar 

  62. Geng YJ, Libby P. Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting. Am J Pathol 1995;147(2):251–66.

    PubMed  CAS  Google Scholar 

  63. Pollman MJ, Yamada T, Horiuhi M, Gibbons GH. Vasoactive substances regulate vascular smooth muscle cell apoptosis: countervailing influences of nitric oxide and angiotensin II. Circulation Research 1996;79:748–756.

    Article  PubMed  CAS  Google Scholar 

  64. Geng YJ, Wu Q, Muszynski M, Hansson GK, Libby P. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin1 beta. Arterioscler Thromb Vasc Biol 1996;16(1):19–27.

    Article  PubMed  CAS  Google Scholar 

  65. Pryor WA, Squadrito GL. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995;268(5 Pt 1):L699–722.

    PubMed  CAS  Google Scholar 

  66. Buttery LD, Springall DR, Chester AH, Evans TJ, Standfield EN, Parums DV, Yacoub MH, Polak JM. Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab Invest 1996;75(I):77–85.

    PubMed  CAS  Google Scholar 

  67. Rajagopalan S, Meng SXP, Ramasamy S, Harrison DG, Galis Z. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro: implications for atherosclerotic plaque stability. J. Clin. Invest. 1996; 98: 2572–2579.

    Article  PubMed  CAS  Google Scholar 

  68. Lablanche JM, Grollier G, Lusson JR, Bassand JP, Drobinski G, Bertand B, Battaglia S, Desveaux B, Juilliere Y, et al. Effect of the direct nitric oxide donors linisidomine and molsidomine on angiographic restenosis after coronary balloon angioplasty: The ACCORD study. Circulation 1997;95:83–89.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Harvard Medical School, Brigham and Women’s Hospital, Boston, USA

    Gary H. Gibbons

Authors
  1. Gary H. Gibbons
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Necker University, Paris, France

    Antoine Lafont

  2. Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Eric J. Topol

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Gibbons, G.H. (1997). Vascular Remodeling and Lesion Formation in Restenosis: Implications for Nitric Oxide-Based Therapeutics. 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_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-6079-1_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7785-6

  • Online ISBN: 978-1-4615-6079-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation