DOI QR코드

DOI QR Code

Experimental Tracheal Replacement: Angiogenesis and Null Apoptosis Promote Stenosis

  • Santibanez-Salgado, J. Alfredo (Lung Transplantation Research Unit, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas") ;
  • Sotres-Vega, Avelina (Lung Transplantation Research Unit, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas") ;
  • Gaxiola-Gaxiola, Miguel O. (Pathology and Morphology Department, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas") ;
  • Villalba-Caloca, Jaime (Lung Transplantation Research Unit, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas") ;
  • Lozoya, Karen Bobadilla (Tecnologico de Monterrey) ;
  • Zuniga-Ramos, Joaquin A. (Tecnologico de Monterrey)
  • 투고 : 2020.12.02
  • 심사 : 2021.04.23
  • 발행 : 2021.06.05

초록

Background: Tracheal replacement is a challenge for thoracic surgeons due to stenosis in the trachea-prosthesis anastomosis. We propose that stenosis occurs due to fibrosis as a result of an abnormal healing process, characterized by an increased expression of wound healing growth factors (vascular endothelial growth factor [VEGF], survivin, and CD31), which promote angiogenesis and decrease apoptosis. We analyzed the immunoreactivity of VEGF, survivin, CD31, and caspase-3 in the development of fibrotic stenosis in prosthetic tracheal replacement. Methods: Fourteen dogs were operated on: group I (n=7) received a 6-ring cervical tracheal segment autograft, while in group II (n=7), a 6-ring segment of the cervical trachea was resected and tracheal continuity was restored with a Dacron prosthesis. The follow-up was 3 months. Immunoreactivity studies for VEGF, survivin, CD31, and caspase-3 were performed. A statistical analysis was done using the Wilcoxon signed rank test. Results: Four animals in group I were euthanized on the 10th postoperative day due to autograft necrosis. Three animals completed the study without anastomotic stenosis. Moderate expression of VEGF (p=0.038), survivin (p=0.038), and CD31 (p=0.038) was found. All group II animals developed stenosis in the trachea-prosthesis anastomotic sites. Microscopy showed abundant collagen and neovascularization vessels. Statistically significant immunoreactive expression of VEGF (p=0.015), survivin (p=0.017), and CD31 (p=0.011) was observed. No expression of caspase-3 was found. Conclusion: We found a strong correlation between fibrosis in trachea-prosthesis anastomoses and excessive angiogenesis, moderate to intense VEGF, CD31, and survivin expression, and null apoptotic activity. These factors led to uncontrolled collagen production.

키워드

참고문헌

  1. Grillo HC. Tracheal replacement: a critical review. Ann Thorac Surg 2002;73:1995-2004. https://doi.org/10.1016/S0003-4975(02)03564-6
  2. Etienne H, Fabre D, Gomez Caro A, et al. Tracheal replacement. Eur Respir J 2018;51:1702211. https://doi.org/10.1183/13993003.02211-2017
  3. Delaere P, van Raemdonck D. Tracheal replacement. J Thorac Dis 2016;8(Suppl 2):S186-96.
  4. Udelsman B, Mathisen DJ, Ott HC. A reassessment of tracheal substitutes: a systematic review. Ann Cardiothorac Surg 2018;7:175-82. https://doi.org/10.21037/acs.2018.01.17
  5. Delaere PR, Vranckx JJ, Den Hondt M; Leuven Tracheal Transplant Group. Tracheal allograft after withdrawal of immunosuppressive therapy. N Engl J Med 2014;370:1568-70. https://doi.org/10.1056/NEJMc1315273
  6. Jorge RG, Armengod AC, Caravajal JM. As originally published in 1990: experimental study of a new porous tracheal prosthesis: updated in 1998. Ann Thorac Surg 1998;65:1830-1. https://doi.org/10.1016/S0003-4975(98)00341-5
  7. Tsukada H, Osada H. Experimental study of a new tracheal prosthesis: pored Dacron tube. J Thorac Cardiovasc Surg 2004;127:877-84. https://doi.org/10.1016/S0022-5223(03)01317-5
  8. Nissen NN, Polverini PJ, Koch AE, Volin MV, Gamelli RL, DiPietro LA. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 1998; 152:1445-52.
  9. Wilgus TA, Ferreira AM, Oberyszyn TM, Bergdall VK, Dipietro LA. Regulation of scar formation by vascular endothelial growth factor. Lab Invest 2008;88:579-90. https://doi.org/10.1038/labinvest.2008.36
  10. DeLisser HM, Christofidou-Solomidou M, Strieter RM, et al. Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol 1997;151:671-7.
  11. Breen EC. VEGF in biological control. J Cell Biochem 2007;102: 1358-67. https://doi.org/10.1002/jcb.21579
  12. Sivakumar B, Harry LE, Paleolog EM. Modulating angiogenesis: more vs less. JAMA 2004;292:972-7. https://doi.org/10.1001/jama.292.8.972
  13. O'Connor DS, Schechner JS, Adida C, et al. Control of apoptosis during angiogenesis by surviving expression in endothelial cells. Am J Pathol 2000;156:393-8. https://doi.org/10.1016/S0002-9440(10)64742-6
  14. Ferrero E, Ferrero ME, Pardi R, Zocchi MR. The platelet endothelial cell adhesion molecule-1 (PECAM1) contributes to endothelial barrier function. FEBS Lett 1995;374:323-6. https://doi.org/10.1016/0014-5793(95)01110-Z
  15. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995;267:1456-62. https://doi.org/10.1126/science.7878464
  16. Iskandar ZA, Al-Joudi FS. Expression of survivin in fetal and adult normal tissues of rat. Malays J Pathol 2006;28:101-5.
  17. Mesri M, Morales-Ruiz M, Ackermann EJ, et al. Suppression of vascular endothelial growth factor-mediated endothelial cell protection by survivin targeting. Am J Pathol 2001;158:1757-65. https://doi.org/10.1016/S0002-9440(10)64131-4
  18. Cohen GM. Caspases: the executioners of apoptosis. Biochem J 1997;326(Pt 1):1-16. https://doi.org/10.1042/bj3260001
  19. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med 2009;361:1570-83. https://doi.org/10.1056/NEJMra0901217
  20. Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ, Levin B. bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res 1995;55:237-41.
  21. Lu CD, Altieri DC, Tanigawa N. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 1998;58:1808-12.
  22. Greenhalgh DG. The role of apoptosis in wound healing. Int J Biochem Cell Biol 1998;30:1019-30. https://doi.org/10.1016/S1357-2725(98)00058-2
  23. Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 2000;6:127-34.
  24. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg 1998;176(2A Suppl):26S-38S. https://doi.org/10.1016/S0002-9610(98)00183-4
  25. Mathisen DJ, Grillo HC, Vlahakes GJ, Daggett WM. The omentum in the management of complicated cardiothoracic problems. J Thorac Cardiovasc Surg 1988;95:677-84. https://doi.org/10.1016/S0022-5223(19)35736-8
  26. Zhang QX, Magovern CJ, Mack CA, Budenbender KT, Ko W, Rosengart TK. Vascular endothelial growth factor is the major angiogenic factor in omentum: mechanism of the omentum-mediated angiogenesis. J Surg Res 1997;67:147-54. https://doi.org/10.1006/jsre.1996.4983
  27. Salassa JR, Pearson BW, Payne WS. Gross and microscopical blood supply of the trachea. Ann Thorac Surg 1977;24:100-7. https://doi.org/10.1016/S0003-4975(10)63716-2
  28. Backer CL, Mavroudis C, Holinger LD. Repair of congenital tracheal stenosis. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2002;5:173-86. https://doi.org/10.1053/pcsu.2002.29718
  29. Dodge-Khatami A, Backer CL, Holinger LD, Mavroudis C, Cook KE, Crawford SE. Healing of a free tracheal autograft is enhanced by topical vascular endothelial growth factor in an experimental rabbit model. J Thorac Cardiovasc Surg 2001;122:554-61. https://doi.org/10.1067/mtc.2001.116206
  30. Dodge-Khatami A, Niessen HW, Baidoshvili A, et al. Topical vascular endothelial growth factor in rabbit tracheal surgery: comparative effect on healing using various reconstruction materials and intraluminal stents. Eur J Cardiothorac Surg 2003;23:6-14. https://doi.org/10.1016/S1010-7940(02)00722-4