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Modulating the Proliferative Response to Treat Restenosis After Vascular Injury

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Molecular and Translational Vascular Medicine

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

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Abstract

Percutaneous coronary intervention (PCI) with stent deployment has become a mainstay in the treatment of patients with coronary artery disease. These metallic endoprostheses prevent abrupt artery closure, the major drawback of PCI in the era of transluminal balloon angioplasty. However, the recurrent arterial narrowing at the site of intervention (restenosis) resulting from excessive smooth muscle cell proliferation is a major shortcoming in 15–30% of patients receiving a bare metal stent. The recent introduction of drug-eluting stents that locally deliver high doses of antiproliferative drugs, such as sirolimus and paclitaxel, has revolutionized the field of revascularization owing to a dramatic reduction in the incidence of in-stent restenosis, target lesion revascularization, and major adverse cardiac events. They are, however, limited by an increased risk of late stent thrombosis that forces a long-term oral dual antiplatelet therapy. A key factor contributing to late stent thrombosis after implantation of drug-eluting stents seems to be the apparent incomplete reendothelialization due to the cytostatic and cytotoxic effects that the active drugs exert on the underlying and neighboring endothelial cells. Here we review therapeutic strategies to limit neointimal cell proliferation in animal models of vascular injury; summarize some of the drug-eluting stents that are currently in clinical use; and discuss new approaches under investigation to optimize the efficacy and safety of this technology to improve PCI outcomes.

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References

  1. Grüntzig AR, Senning A, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med. 1979;301(2):61–8.

    PubMed  Google Scholar 

  2. Palmaz JC, Sibbitt RR, Reuter SR, et al. Expandable intraluminal graft: a preliminary study. Radiology. 1985;156(1):73–7.

    PubMed  CAS  Google Scholar 

  3. Schatz RA, Palmaz JC, Tio FO, et al. Balloon-expandable intracoronary stents in the adult dog. Circulation. 1987;76(2):450–7.

    PubMed  CAS  Google Scholar 

  4. Sigwart U, Puel J, Mirkovitch V, et al. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987;316(12):701–6.

    PubMed  CAS  Google Scholar 

  5. Andrés V. Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential. Cardiovasc Res. 2004;63(1):11–21.

    PubMed  Google Scholar 

  6. Dzau VJ, Braun-Dullaeus RC, Sedding DG. Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med. 2002;8(11):1249–56.

    PubMed  CAS  Google Scholar 

  7. Sousa JE, Costa MA, Abizaid A, et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study. Circulation. 2001;103(2):192–5.

    PubMed  CAS  Google Scholar 

  8. Rensing BJ, Vos J, Smits PC, et al. Coronary restenosis elimination with a sirolimus eluting stent: first European human experience with 6-month angiographic and intravascular ultrasonic follow-up. Eur Heart J. 2001;22(22):2125–30.

    PubMed  CAS  Google Scholar 

  9. Serruys PW, Kutryk MJ, Ong AT. Coronary-artery stents. N Engl J Med. 2006;354(5):483–95.

    PubMed  CAS  Google Scholar 

  10. Togni M, Windecker S, Cocchia R, et al. Sirolimus-eluting stents associated with paradoxic coronary vasoconstriction. J Am Coll Cardiol. 2005;46(2):231–6.

    PubMed  CAS  Google Scholar 

  11. Nebeker JR, Virmani R, Bennett CL, et al. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the research on adverse drug events and reports (RADAR) project. J Am Coll Cardiol. 2006;47(1):175–81.

    PubMed  Google Scholar 

  12. Gonzalo N, Barlis P, Serruys PW, et al. Incomplete stent apposition and delayed tissue coverage are more frequent in drug-eluting stents implanted during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction than in drug-eluting stents implanted for stable/unstable angina: insights from optical coherence tomography. JACC Cardiovasc Interv. 2009;2(5):445–52.

    PubMed  Google Scholar 

  13. Bavry AA, Bhatt DL. Appropriate use of drug-eluting stents: balancing the reduction in restenosis with the concern of late thrombosis. Lancet. 2008;371(9630):2134–43.

    PubMed  CAS  Google Scholar 

  14. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005;293(17):2126–30.

    PubMed  CAS  Google Scholar 

  15. Costa MA, Simon DI. Molecular basis of restenosis and drug-eluting stents. Circulation. 2005;111(17):2257–73.

    PubMed  Google Scholar 

  16. Vidal A, Koff A. Cell-cycle inhibitors: three families united by a common cause. Gene. 2000;247(1–2):1–15.

    PubMed  CAS  Google Scholar 

  17. Bonauer A, Boon RA, Dimmeler S. Vascular microRNAs. Curr Drug Targets. 2010;11:943–9.

    PubMed  CAS  Google Scholar 

  18. Davis BN, Hilyard AC, Nguyen PH, et al. Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype. J Biol Chem. 2009;284(6):3728–38.

    PubMed  CAS  Google Scholar 

  19. Liu X, Cheng Y, Zhang S, et al. A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res. 2009;104(4):476–87.

    PubMed  CAS  Google Scholar 

  20. Schwartz RS, Chronos NA, Virmani R. Preclinical restenosis models and drug-eluting stents: Still important, still much to learn. J Am Coll Cardiol. 2004;44(7):1373–85.

    PubMed  CAS  Google Scholar 

  21. Schwartz RS, Edelman ER, Carter A, et al. Drug-eluting stents in preclinical studies: recommended evaluation from a consensus group. Circulation. 2002;106(14):1867–73.

    PubMed  Google Scholar 

  22. Virmani R, Kolodgie FD, Farb A, et al. Drug eluting stents: are human and animal studies comparable? Heart. 2003;89(2):133–8.

    PubMed  CAS  Google Scholar 

  23. Foster KG, Fingar DC. Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. J Biol Chem. 2010;285(19):14071–7.

    PubMed  CAS  Google Scholar 

  24. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011;12(1):21–35.

    PubMed  CAS  Google Scholar 

  25. Marx SO, Jayaraman T, Go LO, et al. Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res. 1995;76(3):412–7.

    PubMed  CAS  Google Scholar 

  26. Poon M, Marx SO, Gallo R, et al. Rapamycin inhibits vascular smooth muscle cell migration. J Clin Invest. 1996;98(10):2277–83.

    PubMed  CAS  Google Scholar 

  27. Wessely R, Blaich B, Belaiba RS, et al. Comparative characterization of cellular and molecular anti-restenotic profiles of paclitaxel and sirolimus. Implications for local drug delivery. Thromb Haemost. 2007;97(6):1003–12.

    PubMed  CAS  Google Scholar 

  28. Luo Y, Marx SO, Kiyokawa H, et al. Rapamycin resistance tied to defective regulation of p27Kip1. Mol Cell Biol. 1996;16(12):6744–51.

    PubMed  CAS  Google Scholar 

  29. Sun J, Marx SO, Chen HJ, et al. Role for p27(Kip1) in vascular smooth muscle cell migration. Circulation. 2001;103(24):2967–72.

    PubMed  CAS  Google Scholar 

  30. Diez-Juan A, Andres V. Coordinate control of proliferation and migration by the p27Kip1/cyclin-dependent kinase/retinoblastoma pathway in vascular smooth muscle cells and fibroblasts. Circ Res. 2003;92(4):402–10.

    PubMed  CAS  Google Scholar 

  31. Castro C, Diez-Juan A, Cortes MJ, et al. Distinct regulation of mitogen-activated protein kinases and p27Kip1 in smooth muscle cells from different vascular beds. A potential role in establishing regional phenotypic variance. J Biol Chem. 2003;278(7):4482–90.

    PubMed  CAS  Google Scholar 

  32. Burke SE, Lubbers NL, Chen YW, et al. Neointimal formation after balloon-induced vascular injury in Yucatan minipigs is reduced by oral rapamycin. J Cardiovasc Pharmacol. 1999;33(6):829–35.

    PubMed  CAS  Google Scholar 

  33. Gallo R, Padurean A, Jayaraman T, et al. Inhibition of intimal thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle. Circulation. 1999;99(16):2164–70.

    PubMed  CAS  Google Scholar 

  34. Jahnke T, Schafer FK, Bolte H, et al. Short-term rapamycin for inhibition of neointima formation after balloon-mediated aortic injury in rats: is there a window of opportunity for systemic prophylaxis of restenosis? J Endovasc Ther. 2005;12(3):332–42.

    PubMed  Google Scholar 

  35. Carter AJ, Aggarwal M, Kopia GA, et al. Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model. Cardiovasc Res. 2004;63(4):617–24.

    PubMed  CAS  Google Scholar 

  36. Carter AJ, Wei W, Gibson L, et al. Segmental vessel wall shear stress and neointimal formation after sirolimus-eluting stent implantation: physiological insights in a porcine coronary model. Cardiovasc Revasc Med. 2005;6(2):58–64.

    PubMed  Google Scholar 

  37. Tepe G, Muschick P, Laule M, et al. Prevention of carotid artery restenosis after sirolimus-coated stent implantation in pigs. Stroke. 2006;37(2):492–4.

    PubMed  CAS  Google Scholar 

  38. Klugherz BD, Llanos G, Lieuallen W, et al. Twenty-eight-day efficacy and phamacokinetics of the sirolimus-eluting stent. Coron Artery Dis. 2002;13(3):183–8.

    PubMed  Google Scholar 

  39. Langeveld B, Roks AJ, Tio RA, et al. Rat abdominal aorta stenting: a new and reliable small animal model for in-stent restenosis. J Vasc Res. 2004;41(5):377–86.

    PubMed  Google Scholar 

  40. Pires NM, van der Hoeven BL, de Vries MR, et al. Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(epsilon-caprolactone) stent cuff. Biomaterials. 2005;26(26):5386–94.

    PubMed  CAS  Google Scholar 

  41. Pires NM, Eefting D, de Vries MR, et al. Sirolimus and paclitaxel provoke different vascular pathological responses after local delivery in a murine model for restenosis on underlying atherosclerotic arteries. Heart. 2007;93(8):922–7.

    PubMed  CAS  Google Scholar 

  42. Barilli A, Visigalli R, Sala R, et al. In human endothelial cells rapamycin causes mTORC2 inhibition and impairs cell viability and function. Cardiovasc Res. 2008;78(3):563–71.

    PubMed  CAS  Google Scholar 

  43. Hayashi S, Yamamoto A, You F, et al. The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy. Am J Pathol. 2009;175(5):2226–34.

    PubMed  CAS  Google Scholar 

  44. Singh R, Cuervo AM. Autophagy in the cellular energetic balance. Cell Metab. 2011;13(5):495–504.

    PubMed  CAS  Google Scholar 

  45. Frey D, Billinger M, Meier P, et al. Endothelialization of sirolimus-eluting stents with slow and extended drug release in the porcine overstretch model. J Invasive Cardiol. 2008;20(12):631–4.

    PubMed  Google Scholar 

  46. Imanishi T, Kobayashi K, Kuki S, et al. Sirolimus accelerates senescence of endothelial progenitor cells through telomerase inactivation. Atherosclerosis. 2006;189(2):288–96.

    PubMed  CAS  Google Scholar 

  47. Nuhrenberg TG, Voisard R, Fahlisch F, et al. Rapamycin attenuates vascular wall inflammation and progenitor cell promoters after angioplasty. FASEB J. 2005;19(2):246–8.

    PubMed  Google Scholar 

  48. Andrés V, Castro C, Campistol JM. Potential role of proliferation signal inhibitors on atherosclerosis in renal transplant patients. Nephrol Dial Transplant. 2006;21 Suppl 3:iii14–7.

    PubMed  Google Scholar 

  49. Carter AJ, Brodeur A, Collingwood R, et al. Experimental efficacy of an everolimus eluting cobalt chromium stent. Catheter Cardiovasc Interv. 2006;68(1):97–103.

    PubMed  Google Scholar 

  50. Garcia-Touchard A, Burke SE, Toner JL, et al. Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks. Eur Heart J. 2006;27(8):988–93.

    PubMed  CAS  Google Scholar 

  51. Tada N, Virmani R, Grant G, et al. Polymer-free biolimus a9-coated stent demonstrates more sustained intimal inhibition, improved healing, and reduced inflammation compared with a polymer-coated sirolimus-eluting cypher stent in a porcine model. Circ Cardiovasc Interv. 2010;3(2):174–83.

    PubMed  CAS  Google Scholar 

  52. Abal M, Andreu JM, Barasoain I. Taxanes: microtubule and centrosome targets, and cell cycle dependent mechanisms of action. Curr Cancer Drug Targets. 2003;3(3):193–203.

    PubMed  CAS  Google Scholar 

  53. Sollott SJ, Cheng L, Pauly RR, et al. Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat. J Clin Invest. 1995;95(4):1869–76.

    PubMed  CAS  Google Scholar 

  54. Axel DI, Kunert W, Goggelmann C, et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997;96(2):636–45.

    PubMed  CAS  Google Scholar 

  55. Wiskirchen J, Schober W, Schart N, et al. The effects of paclitaxel on the three phases of restenosis: smooth muscle cell proliferation, migration, and matrix formation: an in vitro study. Invest Radiol. 2004;39(9):565–71.

    PubMed  CAS  Google Scholar 

  56. Kim DW, Kwon JS, Kim YG, et al. Novel oral formulation of paclitaxel inhibits neointimal hyperplasia in a rat carotid artery injury model. Circulation. 2004;109(12):1558–63.

    PubMed  CAS  Google Scholar 

  57. Herdeg C, Oberhoff M, Baumbach A, et al. Local paclitaxel delivery for the prevention of restenosis: biological effects and efficacy in vivo. J Am Coll Cardiol. 2000;35(7):1969–76.

    PubMed  CAS  Google Scholar 

  58. Wilson GJ, Polovick JE, Huibregtse BA, et al. Overlapping paclitaxel-eluting stents: long-term effects in a porcine coronary artery model. Cardiovasc Res. 2007;76(2):361–72.

    PubMed  CAS  Google Scholar 

  59. Heldman AW, Cheng L, Jenkins GM, et al. Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis. Circulation. 2001;103(18):2289–95.

    PubMed  CAS  Google Scholar 

  60. Wessely R, Schömig A, Kastrati A. Sirolimus and paclitaxel on polymer-based drug-eluting stents: similar but different. J Am Coll Cardiol. 2006;47(4):708–14.

    PubMed  CAS  Google Scholar 

  61. Finkelstein A, McClean D, Kar S, et al. Local drug delivery via a coronary stent with programmable release pharmacokinetics. Circulation. 2003;107(5):777–84.

    PubMed  Google Scholar 

  62. Scheller B, Speck U, Schmitt A, et al. Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation. J Am Coll Cardiol. 2003;42(8):1415–20.

    PubMed  CAS  Google Scholar 

  63. Scheller B, Speck U, Abramjuk C, et al. Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation. 2004;110(7):810–4.

    PubMed  CAS  Google Scholar 

  64. Epstein FH, Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340(23):1801–11.

    Google Scholar 

  65. Xing D, Nozell S, Chen Y-F, et al. Estrogen and mechanisms of vascular protection. Arterioscler Thromb Vasc Biol. 2009;29(3):289–95.

    PubMed  CAS  Google Scholar 

  66. Geraldes P, Sirois MG, Bernatchez PN, et al. Estrogen regulation of endothelial and smooth muscle cell migration and proliferation: Role of p38 and p42/44 mitogen-activated protein kinase. Arterioscler Thromb Vasc Biol. 2002;22(10):1585–90.

    PubMed  CAS  Google Scholar 

  67. Geraldes P, Sirois MG, Tanguay J-F. Specific contribution of estrogen receptors on mitogen-activated protein kinase pathways and vascular cell activation. Circ Res. 2003;93(5):399–405.

    PubMed  CAS  Google Scholar 

  68. Cheng B, Song J, Zou Y, et al. Responses of vascular smooth muscle cells to estrogen are dependent on balance between ERK and p38 MAPK pathway activities. Int J Cardiol. 2009;134(3):356–65.

    PubMed  Google Scholar 

  69. Kappert K, Caglayan E, Huntgeburth M, et al. 17Beta-estradiol attenuates PDGF signaling in vascular smooth muscle cells at the postreceptor level. Am J Physiol Heart Circ Physiol. 2006;290(2):H538–46.

    PubMed  CAS  Google Scholar 

  70. Krasinski K, Spyridopoulos I, Asahara T, et al. Estradiol accelerates functional endothelial recovery after arterial injury. Circulation. 1997;95(7):1768–72.

    PubMed  CAS  Google Scholar 

  71. Toutain CE, Filipe C, Billon A, et al. Estrogen receptor alpha expression in both endothelium and hematopoietic cells is required for the accelerative effect of estradiol on reendothelialization. Arterioscler Thromb Vasc Biol. 2009;29(10):1543–50.

    PubMed  CAS  Google Scholar 

  72. Filipe C, Lam Shang Leen L, Brouchet L, et al. Estradiol accelerates endothelial healing through the retrograde commitment of uninjured endothelium. Am J Physiol Heart Circ Physiol. 2008;294(6):H2822–30.

    PubMed  CAS  Google Scholar 

  73. Iwakura A, Luedemann C, Shastry S, et al. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation. 2003;108(25):3115–21.

    PubMed  CAS  Google Scholar 

  74. Chen S-J, Li H, Durand J, et al. Estrogen reduces myointimal proliferation after balloon injury of rat carotid artery. Circulation. 1996;93(3):577–84.

    PubMed  CAS  Google Scholar 

  75. Iafrati MD, Karas RH, Aronovitz M, et al. Estrogen inhibits the vascular injury response in estrogen receptor-deficient mice. Nat Med. 1997;3(5):545–8.

    PubMed  CAS  Google Scholar 

  76. Sullivan Jr TR, Karas RH, Aronovitz M, et al. Estrogen inhibits the response-to-injury in a mouse carotid artery model. J Clin Invest. 1995;96(5):2482.

    PubMed  CAS  Google Scholar 

  77. Levine RL, Chen S-J, Durand J, et al. Medroxyprogesterone attenuates estrogen-mediated inhibition of neointima formation after balloon injury of the rat carotid artery. Circulation. 1996;94(9):2221–7.

    PubMed  CAS  Google Scholar 

  78. Oparil S, Levine RL, Chen S-J, et al. Sexually dimorphic response of the balloon-injured rat carotid artery to hormone treatment. Circulation. 1997;95(5):1301–7.

    PubMed  CAS  Google Scholar 

  79. Bakir S, Mori T, Durand J, et al. Estrogen-induced vasoprotection is estrogen receptor dependent: evidence from the balloon-injured rat carotid artery model. Circulation. 2000;101(20):2342–4.

    PubMed  CAS  Google Scholar 

  80. Mori T, Durand J, Chen Y-F, et al. Effects of short-term estrogen treatment on the neointimal response to balloon injury of rat carotid artery. Am J Cardiol. 2000;85(10):1276–9.

    PubMed  CAS  Google Scholar 

  81. Hanke H, Hanke S, Bruck B, et al. Inhibition of the protective effect of estrogen by progesterone in experimental atherosclerosis. Atherosclerosis. 1996;121(1):129–38.

    PubMed  CAS  Google Scholar 

  82. Foegh ML, Asotra S, Howell MH, et al. Estradiol inhibition of arterial neointimal hyperplasia after balloon injury. J Vasc Surg. 1994;19(4):722–6.

    PubMed  CAS  Google Scholar 

  83. White CR, Shelton J, Chen S-J, et al. Estrogen restores endothelial cell function in an experimental model of vascular injury. Circulation. 1997;96(5):1624–30.

    PubMed  CAS  Google Scholar 

  84. Chandrasekar B, Tanguay J-F. Local delivery of 17-beta-estradiol decreases neointimal hyperplasia after coronary angioplasty in a porcine model. J Am Coll Cardiol. 2000;36(6):1972–8.

    PubMed  CAS  Google Scholar 

  85. New G, Moses JW, Roubin GS, et al. Estrogen-eluting, phosphorylcholine-coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model. Catheter Cardiovasc Interv. 2002;57(2):266–71.

    PubMed  Google Scholar 

  86. Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2008;14(1):37–44.

    PubMed  CAS  Google Scholar 

  87. Jaschke B, Michaelis C, Milz S, et al. Local statin therapy differentially interferes with smooth muscle and endothelial cell proliferation and reduces neointima on a drug-eluting stent platform. Cardiovasc Res. 2005;68(3):483–92.

    PubMed  CAS  Google Scholar 

  88. Ruef J, Meshel AS, Hu Z, et al. Flavopiridol inhibits smooth muscle cell proliferation in vitro and neointimal formation in vivo after carotid injury in the rat. Circulation. 1999;100(6):659–65.

    PubMed  CAS  Google Scholar 

  89. Jaschke B, Milz S, Vogeser M, et al. Local cyclin-dependent kinase inhibition by flavopiridol inhibits coronary artery smooth muscle cell proliferation and migration: implications for the applicability on drug-eluting stents to prevent neointima formation following vascular injury. FASEB J. 2004;11:1285–7.

    Google Scholar 

  90. Sung C-P, Arleth AJ, Ohlstein EH. Carvedilol inhibits vascular smooth muscle cell proliferation. J Cardiovasc Pharmacol. 1993;21(2):221–7.

    PubMed  CAS  Google Scholar 

  91. Ohlstein EH, Douglas SA, Sung CP, et al. Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury. Proc Natl Acad Sci U S A. 1993;90(13):6189–93.

    PubMed  CAS  Google Scholar 

  92. Kim W, Jeong MH, Cha KS, et al. Effect of anti-oxidant (carvedilol and probucol) loaded stents in a porcine coronary restenosis model. Circ J. 2005;69(1):101–6.

    PubMed  CAS  Google Scholar 

  93. Miyauchi K, Aikawa M, Tani T, et al. Effect of probucol on smooth muscle cell proliferation and dedifferentiation after vascular injury in rabbits: possible role of PDGF. Cardiovasc Drugs Ther. 1998;12(3):251–60.

    PubMed  CAS  Google Scholar 

  94. Lau AK, Leichtweis SB, Hume P, et al. Probucol promotes functional reendothelialization in balloon-injured rabbit aortas. Circulation. 2003;107(15):2031–6.

    PubMed  CAS  Google Scholar 

  95. Tanous D, Bräsen JH, Choy K, et al. Probucol inhibits in-stent thrombosis and neointimal hyperplasia by promoting re-endothelialization. Atherosclerosis. 2006;189(2):342–9.

    PubMed  CAS  Google Scholar 

  96. Jackson CL, Pettersson KS. Effects of probucol on rat carotid artery responses to balloon catheter injury. Atherosclerosis. 2001;154(2):407–14.

    PubMed  CAS  Google Scholar 

  97. Yokoyama T, Miyauchi K, Kurata T, et al. Effect of probucol on neointimal thickening in a stent porcine restenosis model. Jpn Heart J. 2004;45(2):305–13.

    PubMed  CAS  Google Scholar 

  98. Takahashi S, Oida K, Fujiwara R, et al. Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture. J Cardiovasc Pharmacol. 1992;20(6):900–6.

    PubMed  CAS  Google Scholar 

  99. Hayashi S, Morishita R, Matsushita H, et al. Cyclic AMP inhibited proliferation of human aortic vascular smooth muscle cells, accompanied by induction of p53 and p21. Hypertension. 2000;35(1):237–43.

    PubMed  CAS  Google Scholar 

  100. Aoki M, Morishita R, Hayashi S, et al. Inhibition of neointimal formation after balloon injury by cilostazol, accompanied by improvement of endothelial dysfunction and induction of hepatocyte growth factor in rat diabetes model. Diabetologia. 2001;44(8):1034–42.

    PubMed  CAS  Google Scholar 

  101. Tsuchikane E, Suzuki T, Katoh O. Examination of anti-intima hyperplastic effect on cilostazol-eluting stent in a porcine model. J Invasive Cardiol. 2007;19(3):109–12.

    PubMed  Google Scholar 

  102. Lee C-S, Kwon Y-W, Yang H-M, et al. New mechanism of rosiglitazone to reduce neointimal hyperplasia: activation of glycogen synthase kinase-3beta followed by inhibition of MMP-9. Arterioscler Thromb Vasc Biol. 2009;29(4):472–9.

    PubMed  CAS  Google Scholar 

  103. Phillips JW, Barringhaus KG, Sanders JM, et al. Rosiglitazone reduces the accelerated neointima formation after arterial injury in a mouse injury model of type 2 diabetes. Circulation. 2003;108(16):1994–9.

    PubMed  Google Scholar 

  104. Desouza CV, Murthy SN, Diez J, et al. Differential effects of peroxisome proliferator activator receptor-alpha and gamma ligands on intimal hyperplasia after balloon catheter-induced vascular injury in Zucker rats. J Cardiovasc Pharmacol Ther. 2003;8(4):297–305.

    PubMed  CAS  Google Scholar 

  105. Alessi A, FranÇa Neto O, Brofman P, et al. Use of rosiglitazone before and after vascular injury in hypercholesterolemic rabbits: assessment of neointimal formation. Thromb J. 2008;6(1):12.

    PubMed  Google Scholar 

  106. Joner M, Farb A, Cheng Q, et al. Pioglitazone inhibits in-stent restenosis in atherosclerotic rabbits by targeting transforming growth factor-beta and MCP-1. Arterioscler Thromb Vasc Biol. 2007;27(1):182–9.

    PubMed  CAS  Google Scholar 

  107. Kasai T, Miyauchi K, Yokoyama T, et al. Pioglitazone attenuates neointimal thickening via suppression of the early inflammatory response in a porcine coronary after stenting. Atherosclerosis. 2008;197(2):612–9.

    PubMed  CAS  Google Scholar 

  108. Miyazawa K, Kikuchi S, Fukuyama J, et al. Inhibition of PDGF- and TGF-[beta]1-induced collagen synthesis, migration and proliferation by tranilast in vascular smooth muscle cells from spontaneously hypertensive rats. Atherosclerosis. 1995;118(2):213–21.

    PubMed  CAS  Google Scholar 

  109. Miyazawa K, Hamano S, Ujiie A. Antiproliferative and c-myc mRNA suppressive effect of tranilast on newborn human vascular smooth muscle cells in culture. Br J Pharmacol. 1996;118(4):915.

    PubMed  CAS  Google Scholar 

  110. Watanabe S, Matsuda A, Suzuki Y, et al. Inhibitory mechanism of tranilast in human coronary artery smooth muscle cells proliferation, due to blockade of PDGF-BB-receptors. Br J Pharmacol. 2000;130(2):307–14.

    PubMed  CAS  Google Scholar 

  111. Tanaka K, Honda M, Kuramochi T, et al. Prominent inhibitory effects of tranilast on migration and proliferation of and collagen synthesis by vascular smooth muscle cells. Atherosclerosis. 1994;107(2):179–85.

    PubMed  CAS  Google Scholar 

  112. Sata M, Takahashi A, Tanaka K, et al. Mouse genetic evidence that tranilast reduces smooth muscle cell hyperplasia via a p21(WAF1)-dependent pathway. Arterioscler Thromb Vasc Biol. 2002;22(8):1305–9.

    PubMed  CAS  Google Scholar 

  113. Fukuyama J, Ichikawa K, Miyazawa K, et al. Tranilast suppresses intimal hyperplasia in the balloon injury model and cuff treatment model in rabbits. Jpn J Pharmacol. 1996;70(4):321.

    PubMed  CAS  Google Scholar 

  114. Fukuyama J, Ichikawa K, Hamano S, et al. Tranilast suppresses the vascular intimal hyperplasia after balloon injury in rabbits fed on a high-cholesterol diet. Eur J Pharmacol. 1996;318(2–3):327–32.

    PubMed  CAS  Google Scholar 

  115. Miyazawa N, Umemura K, Kondo K, et al. Effects of pemirolast and tranilast on intimal thickening after arterial injury in the rat. J Cardiovasc Pharmacol. 1997;30(2):157–62.

    PubMed  CAS  Google Scholar 

  116. Kikuchi S, Umemura K, Kondo K, et al. Tranilast suppresses intimal hyperplasia after ­photochemically induced endothelial injury in the rat. Eur J Pharmacol. 1996;295(2–3):221–7.

    PubMed  CAS  Google Scholar 

  117. Ward MR, Agrotis A, Kanellakis P, et al. Tranilast prevents activation of transforming growth factor-beta system, leukocyte accumulation, and neointimal growth in porcine coronary arteries after stenting. Arterioscler Thromb Vasc Biol. 2002;22(6):940–8.

    PubMed  CAS  Google Scholar 

  118. Ishiwata S, Verheye S, Robinson KA, et al. Inhibition of neointima formation by tranilast in pig coronary arteries after balloon angioplasty and stent implantation. J Am Coll Cardiol. 2000;35(5):1331–7.

    PubMed  CAS  Google Scholar 

  119. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360(10):961–72.

    PubMed  CAS  Google Scholar 

  120. Kim YH, Park SW, Lee CW, et al. Comparison of sirolimus-eluting stent, paclitaxel-eluting stent, and bare metal stent in the treatment of long coronary lesions. Catheter Cardiovasc Interv. 2006;67(2):181–7.

    PubMed  Google Scholar 

  121. Colmenarez HJ, Escaned J, Fernandez C, et al. Efficacy and safety of drug-eluting stents in chronic total coronary occlusion recanalization: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55(17):1854–66.

    PubMed  CAS  Google Scholar 

  122. Spaulding C, Henry P, Teiger E, et al. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med. 2006;355(11):1093–104.

    PubMed  CAS  Google Scholar 

  123. Ardissino D, Cavallini C, Bramucci E, et al. Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial. JAMA. 2004;292(22):2727–34.

    PubMed  CAS  Google Scholar 

  124. Holmes Jr DR, Teirstein PS, Satler L, et al. 3-Year follow-up of the SISR (sirolimus-eluting stents versus vascular brachytherapy for in-stent restenosis) trial. JACC Cardiovasc Interv. 2008;1(4):439–48.

    PubMed  Google Scholar 

  125. Latib A, Ferri L, Ielasi A, et al. Comparison of the long-term safety and efficacy of drug-eluting and bare-metal stent implantation in saphenous vein grafts. Circ Cardiovasc Interv. 2010;3(3):249–56.

    PubMed  Google Scholar 

  126. Stenestrand U, James SK, Lindback J, et al. Safety and efficacy of drug-eluting vs. bare metal stents in patients with diabetes mellitus: long-term follow-up in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Eur Heart J. 2010;31(2):177–86.

    PubMed  CAS  Google Scholar 

  127. Sukhija R, Aronow WS, Palaniswamy C, et al. Major adverse cardiac events in patients with moderate to severe renal insufficiency treated with first-generation drug-eluting stents. Am J Cardiol. 2010;105(3):293–6.

    PubMed  CAS  Google Scholar 

  128. Lee MS, Kobashigawa J, Tobis J. Comparison of percutaneous coronary intervention with bare-metal and drug-eluting stents for cardiac allograft vasculopathy. JACC Cardiovasc Interv. 2008;1(6):710–5.

    PubMed  Google Scholar 

  129. Morice MC, Bestehorn HP, Carrie D, et al. Direct stenting of de novo coronary stenoses with tacrolimus-eluting versus carbon-coated carbostents. The randomized JUPITER II trial. EuroIntervention. 2006;2(1):45–52.

    PubMed  Google Scholar 

  130. Verheye S, Agostoni P, Dawkins KD, et al. The GENESIS (randomized, multicenter study of the pimecrolimus-eluting and pimecrolimus/paclitaxel-eluting coronary stent system in patients with de novo lesions of the native coronary arteries) trial. JACC Cardiovasc Interv. 2009;2(3):205–14.

    PubMed  Google Scholar 

  131. Morice M-C, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med. 2002;346(23):1773–80.

    PubMed  CAS  Google Scholar 

  132. Stettler C, Allemann S, Wandel S, et al. Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis. BMJ. 2008;337:a1331.

    PubMed  Google Scholar 

  133. Cassese S, Piccolo R, Galasso G, et al. Twelve-month clinical outcomes of everolimus-eluting stent as compared to paclitaxel- and sirolimus-eluting stent in patients undergoing percutaneous coronary interventions. A meta-analysis of randomized clinical trials. Int J Cardiol. 2011;150:84–9.

    PubMed  Google Scholar 

  134. Adriaenssens T, Mehilli J, Wessely R, et al. Does addition of estradiol improve the efficacy of a rapamycin-eluting stent? Results of the ISAR-PEACE randomized trial. J Am Coll Cardiol. 2007;49(12):1265–71.

    PubMed  CAS  Google Scholar 

  135. Byrne RA, Mehilli J, Iijima R, et al. A polymer-free dual drug-eluting stent in patients with coronary artery disease: a randomized trial vs. polymer-based drug-eluting stents. Eur Heart J. 2009;30(8):923–31.

    PubMed  CAS  Google Scholar 

  136. Grines CL, Bonow RO, Casey Jr DE, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulations. 2007;115(6):813–8.

    Google Scholar 

  137. Wessely R. New drug-eluting stent concepts. Nat Rev. 2010;7(4):194–203.

    CAS  Google Scholar 

  138. Windecker S, Serruys PW, Wandel S, et al. Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial. Lancet. 2008;372(9644):1163–73.

    PubMed  CAS  Google Scholar 

  139. Wessely R, Hausleiter J, Michaelis C, et al. Inhibition of neointima formation by a novel drug-eluting stent system that allows for dose-adjustable, multiple, and on-site stent coating. Arterioscler Thromb Vasc Biol. 2005;25(4):748–53.

    PubMed  CAS  Google Scholar 

  140. Clapper JD, Pearce ME, Guymon CA, et al. Biotinylated biodegradable nanotemplated hydrogel networks for cell interactive applications. Biomacromolecules. 2008;9(4):1188–94.

    PubMed  CAS  Google Scholar 

  141. Erbel R, Di Mario C, Bartunek J, et al. Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial. Lancet. 2007;369(9576):1869–75.

    PubMed  CAS  Google Scholar 

  142. Ormiston JA, Serruys PW, Regar E, et al. A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet. 2008;371(9616):899–907.

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank M.J. Andrés-Manzano for her help with figure preparation. Work in the author’s laboratory is supported by grants from the Spanish Ministry of Science and Innovation (MICINN) (grant SAF2010-16044), Instituto de Salud Carlos III (RECAVA, grant RD06/0014/0021), and the Dr. Léon Dumont Prize 2010 awarded to V.A. by the Belgian Society of Cardiology. C.S.R is the recipient of a predoctoral fellowship from Fundación Mario Losantos del Campo. The CNIC is supported by the MICINN and the Fundación Pro-CNIC.

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  1. Laboratory of Molecular and Genetic Cardiovascular Pathophysiology, Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares – CNIC, C/Melchor Fernández Almagro, 3, Madrid, 28029, Spain

    Vicente Andrés PhD

  2. Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares – CNIC, Madrid, Spain

    José Javier Fuster PhD & Carlos Silvestre-Roig MSc

  3. Department of Cardiology and Angiology, Ev. Bethesda-Johanniter-Klinikum, Duisburg, Germany

    Rainer Wessely MD, PhD

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  1. Vicente Andrés PhD
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  2. José Javier Fuster PhD
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  3. Carlos Silvestre-Roig MSc
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  4. Rainer Wessely MD, PhD
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Correspondence to Vicente Andrés PhD .

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  1. , The University of North Carolina, McAllister Heart Institute, 101 Manning Drive, Chapel Hill, 27599-7525, USA

    Jonathon W. Homeister

  2. , The University of North Carolina, McAllister Heart Institute, 103 Mason Farm Road, Chapel Hill, 27599-7525, USA

    Monte S. Willis

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Andrés, V., Fuster, J.J., Silvestre-Roig, C., Wessely, R. (2012). Modulating the Proliferative Response to Treat Restenosis After Vascular Injury. In: Homeister, J., Willis, M. (eds) Molecular and Translational Vascular Medicine. Molecular and Translational Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-906-8_8

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