Vet Med - Czech, 2020, 65(11):465-472 | DOI: 10.17221/159/2019-VETMED

Adventitial histopathological changes after coronary stenting in a porcine modelOriginal Paper

C Perez-Martinez ORCID...1,2, A Perez de Prado*,2,3, V Caballero-Manso1, M Regueiro-Purrinos2,4, MG de Garnica Garcia5, C Cuellas-Ramon2,3, JM Gonzalo-Orden2,4, M Lopez-Benito2,3, JR Altonaga2,4, T Benito-Gomez2,3, F Fernandez-Vazquez2,3
1 Department of Animal Health, Section of Pathology, Veterinary School, University of León, León, Spain
2 Institute of Biomedicine (IBIOMED), University of León, León, Spain
3 Health Research Foundation in León, León, Spain
4 Department of Veterinary Medicine, Surgery and Anatomy, Section of Surgery, Veterinary School, University of León, León, Spain
5 MicrosVeterinaria SL, León, Spain

The adverse long-term events in first-generation drug-eluting stents were associated with chronic inflammatory response to the polymer. As an alternative, stents with biodegradable polymers emerged, whose effects on the vascular response are not yet fully known. Our objectives were to study the adventitial response to the stent implantation and the role of the polymeric vehicle. A histological (Haematoxylin-Eosin, Verhoeff van Gieson) and immunohistochemical (von Willebrand factor, alpha-smooth muscle actin) analysis were performed on resin-embedded arterial sections from fifteen Large White pigs, 28 days after the random implantation in the coronary arteries of: a chromium-cobalt stent and a stent coated with a permanent polyacrylate or biodegradable poly(D,L)-lactic-co-glycolic polymer, the two latter ones are loaded with sirolimus. Independent of the stent, the adventitial inflammation was associated with the adventitial area (P = 0.006 8) and the inflammation score (P = 0.037 1); and the adventitial actin-positive cells with the vascular damage (P = 0.001 2). A significant relationship was observed between the greater percentages of the restenosis and the more intense inflammation (P = 0.035 1) and the actin-positive cells (P = 0.011 9) in the adventitia. The polymeric vehicle increased the adventitial actin-positive cells (P = 0.018), independent of the type of polymer. The adventitial changes seem to be related to the restenosic process 28 days after the coronary stenting. Further investigations are necessary to confirm the role of the polymeric vehicle on the adventitial histopathological changes.

Keywords: adventitia; pig; polymer; restenosis; stent

Received: November 12, 2019; Accepted: September 16, 2020; Published: November 30, 2020  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Perez-Martinez C, de Prado AP, Caballero-Manso V, Regueiro-Purrinos M, MG de Garnica G, Cuellas-Ramon C, et al.. Adventitial histopathological changes after coronary stenting in a porcine model. Vet Med - Czech. 2020;65(11):465-472. doi: 10.17221/159/2019-VETMED.
Download citation

References

  1. Borhani S, Hassanajili S, Ahmadi Tafti SH, Rabbani S. Cardiovascular stents: Overview, evolution, and next generation. Prog Biomater. 2018 Sep;7(3):175-205. Go to original source... Go to PubMed...
  2. Buccheri D, Piraino D, Andolina G, Cortese B. Understanding and managing in-stent restenosis: A review of clinical data, from pathogenesis to treatment. J Thorac Dis. 2016 Oct;8(10):E1150-62. Go to original source... Go to PubMed...
  3. Chang H, Lei H, Zhao Y, Yang R, Wu A, Mao Y, Huang Y, Lv X, Zhao J, Lou L, Zhang D, He Y, Xu Y, Yang T, Zhao M. Yiqihuoxuejiedu formula restrains vascular remodeling by reducing the inflammation reaction and Cx43 expression in the adventitia after balloon injury. Evid Based Complement Alternat Med. 2015;2015:904273. Go to original source... Go to PubMed...
  4. Christen T, Verin V, Bochaton-Piallat M, Popowski Y, Ramaekers F, Debruyne P, Camenzind E, van Eys G, Gabbiani G. Mechanisms of neointima formation and remodeling in the porcine coronary artery. Circulation. 2001 Feb 13;103(6):882-8. Go to original source... Go to PubMed...
  5. Estevez-Loureiro R, Perez de Prado A, Perez-Martinez C, Cuellas-Ramon C, Regueiro-Purrinos M, Gonzalo-Orden JM, Lopez-Benito M, Molina-Crisol M, DuocastellaCodina L, Fernandez-Vazquez F. Safety and efficacy of new sirolimus-eluting stent models in a preclinical study. Rev Esp Cardiol (Engl Ed). 2015 Dec;68(12):1118-24. Go to original source... Go to PubMed...
  6. Fleenor BS, Bowles DK. Negligible contribution of coronary adventitial fibroblasts to neointimal formation following balloon angioplasty in swine. Am J Physiol Heart Circ Physiol. 2009 May;296(5):H1532-9. Go to original source... Go to PubMed...
  7. Goel SA, Guo LW, Liu B, Kent KC. Mechanisms of postintervention arterial remodelling. Cardiovasc Res. 2012 Dec 1;96(3):363-71. Go to original source... Go to PubMed...
  8. Hofma SH, Whelan DM, van Beusekom HM, Verdouw PD, van der Giessen WJ. Increasing arterial wall injury after long-term implantation of two types of stent in a porcine coronary model. Eur Heart J. 1998 Apr;19(4):601-9. Go to original source... Go to PubMed...
  9. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans: Delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006 Jul 4;48(1): 193-202. Go to original source... Go to PubMed...
  10. Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB. In-stent restenosis: Contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol. 1998 Jan;31(1):224-30. Go to original source... Go to PubMed...
  11. Maiellaro K, Taylor WR. The role of the adventitia in vascular inflammation. Cardiovasc Res. 2007 Sep;75(4):640-8. Go to original source... Go to PubMed...
  12. McMahon S, Bertollo N, O'Cearbhaill ED, Salber J, Pierucci L, Duffy P, Durig T, Bi V, Wang W. Bio-resorbable polymer stents: A review of material progress and prospects. Prog Polym Sci. 2018;83:79-96. Go to original source...
  13. Mulligan-Kehoe MJ, Simons M. Vasa vasorum in normal and diseased arteries. Circulation. 2014 Jun 17;129(24): 2557-66. Go to original source... Go to PubMed...
  14. Natsuaki M, Kozuma K, Morimoto T, Kadota K, Muramatsu T, Nakagawa Y, Akasaka T, Igarashi K, Tanabe K, Morino Y, Ishikawa T, Nishikawa H, Awata M, Abe M, Okada H, Takatsu Y, Ogata N, Kimura K, Urasawa K, Tarutani Y, Shiode N, Kimura T; NEXT Investigators. Biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent: A randomized, controlled, noninferiority trial. J Am Coll Cardiol. 2013 Jul 16;62(3):181-90. Go to original source... Go to PubMed...
  15. Nishimiya K, Matsumoto Y, Shindo T, Hanawa K, Hasebe Y, Tsuburaya R, Shiroto T, Takahashi J, Ito K, IshibashiUeda H, Yasuda S, Shimokawa H. Association of adventitial vasa vasorum and inflammation with coronary hyperconstriction after drug-eluting stent implantation in pigs in vivo. Circ J. 2015;79(8):1787-98. Go to original source... Go to PubMed...
  16. Perez de Prado A, Perez-Martinez C, Cuellas C, GonzaloOrden JM, Diego A, Regueiro M, Martinez-Fernandez B, Altonaga JR, Marin Francisco JG, Fernandez-Vazquez F. Preclinical evaluation of coronary stents: Focus on safety issues. Curr Vasc Pharmacol. 2013 Jan;11(1):74-99. Go to original source...
  17. Perez de Prado A, Perez Martinez C, Cuellas Ramon C, Regueiro Purrinos M, Lopez Benito M, Gonzalo Orden JM, Rodriguez Altonaga JA, Estevez Loureiro R, Benito Gonzalez T, Vinuela Baragano D, Molina Crisol M, Amoros Aguilar M, Perez Serranos I, Vidal Parreu A, Benavides Montegordo A, Duocastella Codina L, Fernandez Vazquez F. Safety and efficacy of new biodegradable polymerbased sirolimus-eluting stents in a preclinical model. Rev Esp Cardiol (Engl Ed). 2017 Dec;70(12):1059-66. Go to original source... Go to PubMed...
  18. Perkins LEL, Rippy MK. Balloons and stents and scaffolds: Preclinical evaluation of interventional devices for occlusive arterial disease. Toxicol Pathol. 2019 Apr;47(3): 297-310. Go to original source... Go to PubMed...
  19. Sangiorgi G, Taylor AJ, Farb A, Carter AJ, Edwards WD, Holmes DR, Schwartz RS, Virmani R. Histopathology of postpercutaneous transluminal coronary angioplasty remodeling in human coronary arteries. Am Heart J. 1999 Oct;138(4 Pt 1):681-7. Go to original source... Go to PubMed...
  20. Schwartz SM, Majesky MW, Murry CE. The intima: Development and monoclonal responses to injury. Atherosclerosis. 1995 Dec;118 Suppl:S125-40. Go to original source...
  21. Schwartz RS, Huber KC, Murphy JG, Edwards WD, Camrud AR, Vlietstra RE, Holmes DR. Restenosis and the proportional neointimal response to coronary artery injury: Results in a porcine model. J Am Coll Cardiol. 1992 Feb; 19(2):267-74. Go to original source... Go to PubMed...
  22. Schwartz RS, Edelman E, Virmani R, Carter A, Granada JF, Kaluza GL, Chronos NA, Robinson KA, Waksman R, Weinberger J, Wilson GJ, Wilensky RL. Drug-eluting stents in preclinical studies: Updated consensus recommendations for preclinical evaluation. Circ Cardiovasc Interv. 2008 Oct;1(2):143-53. Go to original source... Go to PubMed...
  23. Shi Y, O'Brien JE, Fard A, Mannion JD, Wang D, Zalewski A. Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries. Circulation. 1996 Oct 1;94(7):1655-64. Go to original source... Go to PubMed...
  24. Sperling C, Waliszewski MW, Kherad B, Krackhardt F. Comparative preclinical evaluation of a polymer-free sirolimus-eluting stent in porcine coronary arteries. Ther Adv Cardiovasc Dis. 2019 Jan-Dec;13:1753944719826335. Go to original source... Go to PubMed...
  25. Stenmark KR, Yeager ME, El Kasmi KC, Nozik-Grayck E, Gerasimovskaya EV, Li M, Riddle SR, Frid MG. The adventitia: Essential regulator of vascular wall structure and function. Annu Rev Physiol. 2013;75:23-47. Go to original source... Go to PubMed...
  26. Tomberli B, Mattesini A, Baldereschi GI, Di Mario C. A brief history of coronary artery stents. Rev Esp Cardiol (Engl Ed). 2018 May;71(5):312-9. Go to original source... Go to PubMed...
  27. Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O, Kolodgie FD. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: Should we be cautious? Circulation. 2004 Feb 17;109(6):701-5. Go to original source... Go to PubMed...
  28. van der Giessen WJ, Lincoff AM, Schwartz RS, van Beusekom HM, Serruys PW, Holmes DR Jr, Ellis SG, Topol EJ. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation. 1996 Oct 1;94(7):1690-7. Go to original source... Go to PubMed...

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY NC 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.