Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC mMPcppc5XjqZWzszsZrRXXb S0066-782X2019000100011 10.5935/abc.20180269 Short Editorial Synergy of Rapamycin and Cyanoacrylate in Reducing Intimal Hyperplasia 0000-0002-5556-8061 Koike Marcia Kiyomi Universidade de São Paulo São Paulo SP Brazil Universidade de São Paulo, São Paulo, SP - Brazil Mailing Address: Marcia Kiyomi Koike, Av. Dr Arnaldo, 455, sala 3189 - CEP 01246-903, Cerqueira Cesar, São Paulo, SP - Brasil. email: mkkoike17@gmail.com 1 2019 112 1 11 11 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited Keywords Coronary Artery Diseases Myocardial Revascularization Vascular Diseases Imunosupressive Agents Cianoacrilates Hyperplasia Rats

Myocardial revascularization (CABG) surgery remains one of the main therapies for coronary disease. However, vascular disease that follows CABG remains a challenge to medicine. The mechanical, molecular and cellular changes undergone by the venous vascular graft when inserted into the coronary artery flow culminate in thrombosis, intimal hyperplasia, and atherosclerotic process, and end with restenosis.1,2

CABG experimental models were crucial to the understanding of mechanisms present in the course of vascular disease. The vascular graft model with anastomosis of the external jugular vein with the carotid artery represents an experimental model of vascular disease similar to that occurring after CABG. Pigs, rabbits, and rats may be used in this model because of protocol reproducibility, cost, and benefit.3,4

Strategies interfering with the mechanisms of vascular disease after CABG may reduce venous graft restenosis. Rapamycin, an immunosuppressive, showed antiproliferative effect of vascular smooth muscle cells in experimental models.4,5 Tianshu-Chu et al.,6 in an experimental study in rats that reproduces vascular disease after CABG, demonstrated that the combination of rapamycin and cyanoacrylate showed synergy to prevent intimal thickening. The combination of rapamycin and cyanoacrylate inhibited cell proliferation, primarily of dedifferentiated vascular smooth muscle cells (myofibroblasts) and vascular cells, preventing intimal hyperplasia, extracellular matrix deposition and neoangiogenesis. Thus, the combination of rapamycin with cyanoacrylate shows synergy when compared to the isolated use.

References 1 de Vries MR, Quax PHA. Inflammation in vein graft disease. Front Cardiovasc Med. 2018; 5:3. de Vries MR Quax PHA Inflammation in vein graft disease Front Cardiovasc Med 2018 5 3 3 2 Gooch KJ, Firstenberg MS, Shrefler BS, Scandling BW. Biomechanics and mechanobiology of saphenous vein grafts. J Biomech Eng. 2018; 140(2):020804-020804-16. Gooch KJ Firstenberg MS Shrefler BS Scandling BW Biomechanics and mechanobiology of saphenous vein grafts J Biomech Eng 2018 140 2 020804-020804-16 3 Mylonaki I, Allain E, Strano F, Alle'mann E, Corpataux J-M, Meda P, et al. Evaluating intimal hyperplasia under clinical conditions. Interact Cardiovasc Thorac Surg. 2018;27(3):427-36. Mylonaki I Allain E Strano F Alle'mann E Corpataux J-M Meda P Evaluating intimal hyperplasia under clinical conditions Interact Cardiovasc Thorac Surg 2018 27 3 427 436 4 Chen HL, Liu K, Meng XY, Wen XD, You QS. Local application of rapamycin inhibits vein graft restenosis in rabbits. Transpl Proc. 2011;43(5):2017-21. Chen HL Liu K Meng XY Wen XD You QS Local application of rapamycin inhibits vein graft restenosis in rabbits Transpl Proc 2011 43 5 2017 2021 5 Skalsky I, Szarszoi O, Filova E, Parizek M, Lytvynets A, Maluskova J, et al. A perivascular system releasing sirolimus prevented intimal hyperplasia in a rabbit model in a medium-term study. Int J Phamaceutics. 2012;427(2):311-9. Skalsky I Szarszoi O Filova E Parizek M Lytvynets A Maluskova J A perivascular system releasing sirolimus prevented intimal hyperplasia in a rabbit model in a medium-term study Int J Phamaceutics 2012 427 2 311 319 6 Tianshu-Chu, Congrong-Gao, Zhiwei-zhao, Fei-Ling, Ayu-Sun, Yuanbiao-Zheng, Jing-Cao, et al. Rapamycin combined with a-Cyanoacrylate contributes to inhibiting intimal hyperplasia in rat models. Arq Bras Cardiol. 2019; 112(1):3-10. Tianshu-Chu Congrong-Gao Zhiwei-zhao Fei-Ling Ayu-Sun Yuanbiao-Zheng Jing-Cao Rapamycin combined with a-Cyanoacrylate contributes to inhibiting intimal hyperplasia in rat models Arq Bras Cardiol 2019 112 1 3 10 Minieditorial Sinergia entre Rampamicina e Cianoacrilato na Redução da Hiperplasia Intimal 0000-0002-5556-8061 Koike Marcia Kiyomi Universidade de São Paulo, São Paulo, SP - Brasil Correspondência: Marcia Kiyomi Koike, Av. Dr Arnaldo, 455, sala 3189 - CEP 01246-903, Cerqueira Cesar, São Paulo, SP - Brasil. email: mkkoike17@gmail.com Palavras-chave Doença da Artéria Coronariana Revascularização do Miocárdio Doenças Vasculares Imunossupressores Cianoacrilatos Proliferação Celular Hiperplasia Ratos

A cirurgia de revascularização miocárdica (CRM) se mantém entre os principais tratamentos para doença coronariana. No entanto, a doença vascular que ocorre após a CRM permanece como um desafio à medicina. As alterações mecânicas, moleculares e celulares sofridas pelo enxerto vascular venoso quando inserido no fluxo arterial coronariano culmina em trombose, hiperplasia intimal e processo aterosclerótico e finaliza-se com a reestenose.1,2

Os modelos experimentais da CRM foram fundamentais para compreender os mecanismos presentes durante o curso da doença vascular. O modelo de enxerto vascular com anastomose da veia jugular externa com a carótida representa um modelo experimental de doença vascular semelhante ao que ocorre após a CRM. Porcos, coelhos e ratos podem ser utilizados neste modelo devido à reprodutibilidade do protocolo, custo e benefício.3,4

Estratégias que interferem nos mecanismos da doença vascular após CRM podem reduzir a reestenose do enxerto venoso. A rampamicina, um imunossupressor, mostrou efeito antiproliferativo das células musculares lisas vasculares em modelos experimentais.4,5 Tianshu-Chu et al.,6 em um estudo experimental em ratos que reproduz a doença vascular após CRM, demonstraram que a combinação entre a rampamicina e o cianoacrilato apresentaram sinergia para prevenção do espessamento intimal. A combinação da rampamicina com o cianoacrilato inibiu a proliferação celular principalmente de células musculares lisas vasculares desdiferenciadas (miofibroblastos) e células vasculares, prevenindo a hiperplasia intimal, a deposição intensa de matriz extracelular e a neoangiogenese. Assim, a combinação da rampamicina com o cianoacrilato apresenta uma sinergia quando comparada ao uso isolado.