Abstract
Restenosis, simply defined, is a new lumen narrowing at the site of a previous vascular reconstruction. Restenosis has been a major limitation of surgical and endovascular reconstructions since their inception, and while decades of research have yielded vastly improved results for percutaneous coronary interventions (PCI), strategies to eliminate restenosis remain elusive. Increased application of endovascular therapy to extra-coronary beds has been met with sobering rates of late failures. This persistence of the problem reflects our incomplete understanding of its complex pathogenesis, and further research and novel approaches to prevention are needed before the full potential of our interventions can be realized.
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References
Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med. 1994;331:489–95.
Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med. 1994;331:496–501.
Mehran R, Dangas G, Abizaid A, et al. Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. Circulation. 1999;100:1872–8.
Brener SJ, Prasad AJ, Khan Z, Sacchi TJ. The relationship between late lumen loss and restenosis among various drug-eluting stents: a systematic review and meta-regression analysis of randomized clinical trials. Atherosclerosis. 2011;214:158–62.
Moses JW, Leon MB, Popma JJ, et al. Sirolimus-dluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003;349:1315–23.
Schofer J, Schluter M, Gershlick AH, et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomized controlled trial (E-SIRIUS). Lancet. 2003;362:1093–9.
Abizaid A, Costa MA, Blanchard D, et al. Sirolimus-eluting stents inhibit neointimal hyperplasia in diabetic patients. Insights from the RAVEL trail. Eur Heart J. 2004;25:107–12.
Grube E, Silber S, Hauptmann KE, et al. TAXUS I: six-and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation. 2003;107:38–42.
Colombo A, Drzewiecki J, Banning A, et al. Randomized study to assess the effectiveness of slow and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions. Circulation. 2003;108:788–94.
Stone GW, Midei M, Newman W, et al. Randomized comparison so everolimus-eluting and paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronart Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial. Circulation. 2009;119:680–6.
Kedhi E, Joesoef KS, MaFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real life practice (COMPARE): a randomized trial. Lancet. 2010;375:201–9.
Stankovic G, Colombo A, Bersin R, et al. Comparison of directional coronary atherectomy and stenting versus stenting alone for the treatment of de novo and restenotic coronary artery narrowing. Am J Cardiol. 2004;93:953–8.
Bittl JA, Chew DP, Topol EJ, Kong DF, Califf RM. Meta-analysis of randomized trials of percutaneous transluminal coronary angioplasty versus atherectomy, cutting balloon atherotomy, or laser angioplasty. J Am Coll Cardiol. 2004;43:936–42.
Leertouwer TC, Gussenhoven EJ, Bosch JL, et al. Stent placement for renal arterial stenosis: where do we stand? A meta-analysis. Radiology. 2000;216:78–85.
Corriere MA, Edwards MS, Pearce JD, Andrews JS, Geary RL, Hansen KJ. Restenosis after renal artery angioplasty and stenting: incidence and risk factors. J Vasc Surg. 2009;50:813–9.
Zahringer M, Sapoval M, Pattynama PMT, et al. Sirolimus-eluting versus bare-metal low-profile stent for renal artery treatment (GREAT trial): angiographic follow-up after 6 month and clinical outcome up to 2 years. J Endovasc Ther. 2007;14:460–8.
Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Concensus (TASC). J Vasc Surg. 2000;31:S1–296.
Mwipatayi BP, Hockings A, Hofmann M, Garbowski M, Sieunarine K. Balloon angioplasty compared with stenting for treatment of femoropopliteal occlusive disease: a meta-analysis. J Vasc Surg. 2008;47:461–9.
Conte MS. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) and the (hoped for) dawn of evidence-based treatment for advanced limb ischemia. J Vasc Surg. 2010;51(5 Suppl):69S–75.
Becquemin JP, Favre JP, Marzelle J, Nemoz C, Corsin C, Liezorovicz A. Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: a multicenter prospective randomized study. J Vasc Surg. 2003;37:487–94.
Duda SH, Bosiers M, Lammer J, Scheinert D, Zeller T, Oliva V, et al. Drug-eluting and bare nitinol stents for the treatment of atherosclerotic lesions in the superficial femoral artery: long-term results from the SIROCCO trial. J Endovasc Ther. 2006;13:701–10.
McQuade K, Gable D, Hohman S, Pearl G, Theune B. Randomized comparison of ePTFE/nitinol self-expanding stent graft vs prosthetic femoral-popliteal bypass in the treatment of superficial femoral artery occlusive disease. J Vasc Surg. 2009;49:109–15.
Archie Jr JP. A fifteen-year experience with carotid endarterectomy after a formal operative protocol requiring highly frequent patch angioplasty. J Vasc Surg. 2000;31:724–35.
Mantese VA, Timaran CH, Chiu D, Begg RJ, Brott TG, CREST Investigators. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): stenting versus carotid endarterectomy for carotid disease. Stroke. 2010;41(10 Suppl):S31–4.
Lal BK, Brott TG. The Carotid Revascularization Endarterectomy vs. Stenting Trial completes randomization: lessons learned and anticipated results. J Vasc Surg. 2009;50:1224–31.
Tallarita T, Oderich GS, Macedo TA, Gloviczki P, Misra S, Duncan AA, et al. Reinterventions for stent restenosis in patients treated for atherosclerotic mesenteric artery disease. J Vasc Surg. 2011;54:1422–9.
Peck MA, Conrad MF, Kwolek CJ, LaMuraglia GM, Paruchuri V, Cambria RP. Intermediate-term outcomes of endovascular treatment for symptomatic chronic mesenteric ischemia. J Vasc Surg. 2010;51:140–7.
Lee RW, Bakken AM, Palchik E, Saad WE, Davies MG. Long-term outcomes of endoluminal therapy for chronic atherosclerotic occlusive mesenteric disease. Ann Vasc Surg. 2008;22:541–6.
Holmes DR Jr, Vilietstra RE, Smith HC, et al. Restenosis after percutaneous transluminal coronary angioplasty (PTCA): a report from the PTCA Registry of the National Heart, Lung, and Blood Institute. Am J Cardiol. 1984;53:77C–81C; Thornton MA, Gruentzig AR, Hollman J, King SB 3rd, Douglas JS. Coumadin and aspirin in prevention of recurrence after transluminal coronary angioplasty: a randomized study. Circulation. 1984;69:721–727.
Serruys PW, Luijen HE, Beatt KJ, et al. Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months. Circulation. 1988;77:361–71.
Nobuyoshi M, Kimura T, Nosaka H, et al. Restenosis after successful percutaneous transluminal coronary angioplasty: serial angiographic follow-up of 229 patients. J Am Coll Cardiol. 1988;12:616–23.
Faxon DP, Spiro TE, Minor S, for the ERA Investigators. Low molecular weight heparin in prevention of restenosis after angioplasty: results of enoxaparin restenosis (ERA) trial. Circulation. 1994;90:908–14.
MERCATOR Study Group. Does the new angiotensin converting enzyme inhibitor cilazapril prewent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial. Circulation. 1992;86:100–10.
Khan MM, Ellis SG, Aguirre FV, Weisman HF, Wildermann NM, Califf RM, et al. Does intracoronary thrombus influence the outcome of high risk percutaneous transluminal coronary angioplasty? Clinical and angiographic outcomes in a large multicenter trial. EPIC Investigators. Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing Ischemic Complications. J Am Coll Cardiol. 1998;31:31–6.
Kastrati A, Mehilli J, von Beckerath N, et al. Sirolimus-eluting stent or paclitaxel-eluting stents vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial. JAMA. 2005;293:165–71.
Lal BK, Beach KW, Roubin GS, et al. CREST Investigators. Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial. Lancet Neurol. 2012;11(9):755–63.
Schillinger M, Sabeti S, Dick P, Amighi J, Mlekusch W, Schlager O, et al. Sustained benefit at 2 years of primary femoropopliteal stenting compared with balloon angioplasty with optional stenting. Circulation. 2007;115:2745–9.
Moliterno DJ, Topol EJ. Restenosis: epidemiology and treatment. In: Topol EJ, editor. Textbook of cardiovascular medicine. 2nd ed. Philadelphia: Lippincott-Raven; 2002. p. 1715–50.
Geary RL, Koyama N, Wang TW, Vergel S, Clowes AW. Failure of heparin to inhibit inrimal hyperplasia in injured baboon arteries: the role of heparin-sensitive and heparini-insensitive pathways in the stimulation of smooth muscle cell migration and proliferation. Circulation. 1995;91:2972–81.
Geary RL, Williams JK, Golden D, Brown DG, Benjamin ME, Adams MR. Time course of cellular proliferation, intimal hyperplasia, and remodeling following angioplasty in monkeys with established atherosclerosis: a nonhuman primate model of restenosis. Arterioscler Thromb Vasc Biol. 1996;16:34–43.
Mintz GS, Popma JJ, Pichard AD, et al. Arterial remodeling after coronary angioplasty. A serial intravascular ultrasound study. Circulation. 1996;94:35–43.
Lansky AJ, Mintz GS, Popma JJ, et al. Remodeling after directional coronary atherectomy (with and without adjuct percutaneous transluminal coronary antioplasty): a serial angiographic and intravascular ultrasound analysis from the Optimal Atherectomy Restenosis Study. J Am Coll Cardiol. 1998;32:329–37.
Pasterkamp G, Mali WP, Borst C. Application of intravascular ultrasound in remodeling studies. Semin Interv Cardiol. 1997;2:11–8.
Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest. 1983;49:327–33.
Clowes AW, Reidy MA, Clowes MM. Mechanisms of stenosis after arterial injury. Lab Invest. 1983;49:208–15.
Clowes AW, Schwartz SM. Significance of quiescent smooth muscle migration in the injured rat carotid artery. Circ Res. 1985;56:139–45.
Cooke JP, Ghebremariam YT. Dietary nitrate, nitric oxide, and restenosis. J Clin Invest. 2011;121:1258–60.
Majesky MW, Schwartz SM, Clowes MM, Clowes AW. Heparin regulates smooth muscle S phase entry in the injured rat carotid artery. Circ Res. 1987;61:296–300.
Deutsch M, Meinhart J, Zilla P, Howanietz N, Gorlitzer M, Froeschl A, et al. Long-term experience in autologous in vitro endothelialization of infrainguinal ePTFE grafts. J Vasc Surg. 2009;49:352–62.
Miglionico M, Patti G, D’Ambrosio A, Di Sciascio G. Percutaneous coronary intervention utilizing a new endothelial progenitor cells antibody-coated stent: a prospective single-center registry in high-risk patients. Catheter Cardiovasc Interv. 2008;71:600–4.
Powell JS, Clozel JP, Muller EKM, et al. Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science. 1989;245:186–8.
Daemen MJAP, Lombardi DM, Bosman FT, Schwartz SM. Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res. 1991;68:450–6.
Mondy JS, Williams JK, Adams MR, Dean RH, Geary RL. Structural determinants of lumen narrowing after angioplasty in atherosclerotic nonhuman primates. J Vasc Surg. 1997;26:875–83.
Geary RL, Nikkari ST, Wagner WD, Williams JK, Adams MR, Dean RH. Wound healing: a paradigm for lumen narrowing following arterial reconstruction. J Vasc Surg. 1998;27:96–108.
Martin P. Wound healing-aiming at perfect skin regeneration. Science. 1997;276:75–81.
Gabbiani G, Hirshcel BJ, Ryan GB, Statkov PR, Majno G. Granulation tissue as a contractile organ. J Exp Med. 1972;135:719–33.
Scott PG, Dodd CM, Tredget EE, Ghahary A, Rahemtulla F. Immunohistochemical localization of the proteoglycans decorin, biglycan and versican and transforming growth factor-β in human post-burn hypertrophic and mature scars. Histopathology. 1995;26:423–31.
Inoue T, Uchida T, Yaguchi I, Sakai Y, Takayanagi K, Morooka S. Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis. Circulation. 2003;107:1757–63.
Biasucci LM, Liuzzo G, Buffon A, Maseri A. The variable role of inflammation in acute coronary syndromes and in restenosis. Semin Interv Cardiol. 1999;4:105–10.
Nikkari ST, Jarvelainen HT, Wight TN, Ferguson M, Clowes AW. Smooth muscle cell expression of extracellular matrix genes after arterial injury. Am J Pathol. 1994;144:1348–56.
Raines EW. The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease. Int J Exp Pathol. 2000;81:173–82.
Wight TN, Merrilees MJ. Proteoglycans in atherosclerosis and restenosis: key roles for versican. Circ Res. 2004;94:1158–67.
Hedin U, Roy J, Tran PK, Lundmark K, Rahman A. Control of smooth muscle cell proliferation—the role of the basement membrane. Thromb Haemost. 1999;82 Suppl 1:23–6.
Riessen R, Wight TN, Pastore C, Henley C, Isner JM. Distribution of hyaluronan during extracellular matrix remodeling in human restenotic arteries and balloon-injured rat carotid arteries. Circulation. 1996;93:1141–7.
Fraser JRE, Laurent TC, Laurent UBG. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med. 1997;242:27–33.
Knudson CB, Knudson W. Hyaluronan-binding proteins in development, tissue homeostasis, and disease. FASEB J. 1993;7:1233–41.
Price RD, Myers S, Leigh IM, Navsaria HA. The role of hyaluronic acid in wound healing: assessment of clinical evidence. Am J Clin Dermatol. 2005;6:393–402.
Oksalo O, Salo T, Tammi R, et al. Expression of proteoglycans and hyaluronan during wound healing. J Histochem Cytochem. 1995;43:125–35.
Travis JA, Hughes MG, Wong JM, Wagner WD, Geary RL. Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: role of CD44 and implications for constrictive remodeling. Circ Res. 2001;88:77–83.
Jain M, He Q, Lee WS, et al. Role of CD44 in the reaction of vascular smooth muscle cells to arterial wall injury. J Clin Invest. 1996;97:596–603.
Courtman DW, Franco CD, Meng Q, Bendeck MP. Inwark remodeling of the rabbit aorta is blocked by the matrix metalloproteinase inhibitor doxycycline. J Vasc Res. 2004;41:157–65.
de Smet BJ, de Kleijn D, Hanemaaijer R, et al. Metalloproteinase inhibition reduces constrictive arterial remodeling after balloon angioplasty: a study in the atherosclerotic Yucatan micropig. Circulation. 2000;101:2962–7.
Cherr GS, Motew SJ, Travis JA, et al. Metalloproteinase inhibition and the response to angioplasty and stenting in atherosclerotic primates. Arterioscler Thromb Vasc Biol. 2002;22:161–6.
Araujo CM, Rando GA, Mauro MF, Cristóvão SA, Sanchez IS, Salman AA, et al. Batimastat-eluting stent implantation for the treatment of coronary artery disease: results of the Brazilian pilot study. Arq Bras Cardiol. 2005;84:256–60.
Leite PF, Danilovic A, Moriel P, et al. Sustained decrease in superoxide dismutase activity underlies constrictive remodeling after balloon injury in rabbits. Arterioscler Thromb Vasc Biol. 2003;23:2197–202.
Daniels JT, Schultz GS, Blalock TD, et al. Mediation of transforming growth factor-beta(1)- stimulated matrix contraction by fibroblasts: a role for connective tissue growth factor in contractile scarring. Am J Pathol. 2003;163:2043–52.
Geary RL, Wong JM, Rossini A, Schwartz SM, Adams LD. Expression profiling identifies 147 genes contributing to an unique primate neointimal smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol. 2002;22:2010–6.
Kingston PA, Sinha S, Appleby CE, et al. Adenovirus-mediated gene transfer of transforming growth factor-beta3, but not transforming growth factor-beta1, inhibits constrictive remodeling and reduces luminal loss after coronary angioplasty. Circulation. 2003;108:2819–25.
Ryan ST, Koteliansky VE, Gotwals PJ, Lindner V. Transforming growth factor-beta-dependent events in vascular remodeling following arterial injury. J Vasc Res. 2003;40:37–46.
Zeller T, Muller C, Frank U, et al. Gold coating and restenosis after primary stenting of ostial renal artery stenosis. Catheter Cardiovasc Interv. 2003;60:1–6.
Sacks D, Marinelli DL, Martin LG, et al. Reporting standards for clinical evaluation of new peripheral arterial revascularization devices. Technology Assessment Committee. J Vasc Interv Radiol. 1997;8:137–49.
Iida O, Uematsu M, Soga Y, Hirano K, Suzuki K, Yokoi H, et al. Timing of the restenosis following nitinol stenting in the superficial femoral artery and the factors associated with early and late restenoses. Catheter Cardiovasc Interv. 2011;78:611–7.
Lammer J, Bosiers M, Zeller T, Schillinger M, Boone E, Zaugg MJ, et al. First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease. J Vasc Surg. 2011;54:394–401.
Serruys PW, Ormiston JA, Onuma Y, et al. A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods. Lancet. 2009;373:897–910.
Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31.
Walter DH, Cejna M, Diaz-Sandoval L, et al. Local gene transfer of phvegf-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis. Circulation. 2004;110:36–45.
Schober A, Hoffmann R, Opree N, et al. Peripheral cd34+ cells and the risk of in-stent restenosis in patients with coronary heart disease. Am J Cardiol. 2005;96:1116–22.
Aoki J, Serruys PW, van Beusekom H, et al. Endothelial progenitor cell capture by stents coated with antibody against CD34: the Healing-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First in Man) Regestry. J Am Coll Cardiol. 2005;45:1574–9.
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Ma, X., Geary, R.L. (2013). Arterial Wall Remodeling and Restenosis Following Vascular Reconstruction. In: Gabriel, E., Gabriel, S. (eds) Inflammatory Response in Cardiovascular Surgery. Springer, London. https://doi.org/10.1007/978-1-4471-4429-8_14
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