화학공학소재연구정보센터
Macromolecular Research, Vol.22, No.3, 272-278, March, 2014
Radiolabeled Chitosan Hydrogel Containing VEGF Enhances Angiogenesis in a Rodent Model of Acute Myocardial Infarction
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Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis in an infarcted myocardium. The purpose of the current investigation was to validate whether a radiolabeled VEGF delivery system can be effectively monitored in vivo, and to ascertain whether the growth factor induces an angiogenic effect to facilitate recovery from infarct conditions in rodent myocardial infarction (MI) models. Rat MI models were divided into three groups, one with left anterior descending coronary artery (LAD) ligation with no injection (the control group), one with LAD ligation and I-131 VEGF injection (the VEGF group), and one with LAD ligation and I-131 VEGF-loaded chitosan injection (the VIC group). On day 7 after injection, autoradiography imaging was performed, followed by semiquantitative and histopathologic analyses. In semi-quantitative analysis, the mean anterior-to-inferior wall ratio of the VIC group was significantly higher than those of the control and VEGF groups (p<0.05). Histopathologic experiments revealed a marked increase in microvascular density in the VIC group compared to those of the control and VEGF groups (p<0.05). Intramyocardially injected VIC was not only effectively monitored in vivo, but also stimulated therapeutic angiogenesis in the infarcted myocardium. Our findings support that the developed VIC is a novel theranostic tool to improve myocardial perfusion following myocardial infarction.
  1. Fukuda S, Yoshii S, Kaga S, Matsumoto M, Kugiyama K, Maulik N, Mol. Cell. Biochem., 264, 143 (2004)
  2. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J, Nature., 407, 242 (2000)
  3. Harada K, Friedman M, Lopez JJ, Wang SY, Li J, Prasad PV, Pearlman JD, Edelman ER, Sellke FW, Simons M, Am. J. Physiol., 270, H1791 (1996)
  4. Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ, Shah PK, Willerson JT, Benza RL, Berman DS, Gibson CM, Bajamonde A, Rundle AC, Fine J, McCluskey ER, Circulation., 107, 1359 (2003)
  5. Hughes GC, Biswas SS, Yin B, Coleman RE, DeGrado TR, Landolfo CK, Lowe JE, Annex BH, Landolfo KP, Ann. Thorac. Surg., 77, 812 (2004)
  6. Hariawala MD, Horowitz JR, Esakof D, Sheriff DD, Walter DH, Keyt B, Isner JM, Symes JF, J. Surg. Res., 63, 77 (1996)
  7. Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM, Circulation., 102, 898 (2000)
  8. Yang R, Thomas GR, Bunting S, Ko A, Ferrara N, Keyt B, Ross J, Jin H, J. Cardiovasc. Pharmacol., 27, 838 (1996)
  9. Kean T, Thanou M, Adv. Drug Deliv. Rev., 62, 3 (2010)
  10. Wang JJ, Zeng ZW, Xiao RZ, Xie T, Zhou GL, Zhan XR, Wang SL, Int. J. Nanomedicine., 6, 765 (2011)
  11. Kuntner C, Wanek T, Hoffer M, Dangl D, Hornof M, Kvaternik H, Langer O, Mol. Imaging Biol., 13, 222 (2011)
  12. D'Andrea LD, Del Gatto A, De Rosa L, Romanelli A, Pedone C, Curr. Pharm. Design., 15, 2414 (2009)
  13. Freedman SB, Isner JM, Ann. Intern. Med., 136, 54 (2002)
  14. Helisch A, Schaper W, Z. Kardiol., 89, 239 (2000)
  15. Kornowski R, Fuchs S, Leon MB, Epstein SE, Circulation., 101, 454 (2000)
  16. Laham RJ, Garcia L, Baim DS, Post M, Simons M, Curr. Interv. Cardiol. Rep., 1, 228 (1999)
  17. Yoon YS, Johnson IA, Park JS, Diaz L, Losordo DW, Mol. Cell. Biochem., 264, 63 (2004)
  18. Kwon JS, Park IK, Cho AS, Shin SM, Hong MH, Jeong SY, Kim YS, Min JJ, Jeong MH, Kim WJ, Jo S, Pun SH, Cho JG, Park JC, Kang JC, Ahn Y, J. Control. Release., 138, 168 (2009)
  19. Silva EA, Mooney DJ, J. Thromb. Haemost., 5, 590 (2007)
  20. Wu J, Zeng F, Huang XP, Chung JC, Konecny F, Weisel RD, Li RK, Biomaterials., 32, 579 (2011)
  21. Zhang J, Ding L, Zhao Y, Sun W, Chen B, Lin H, Wang X, Zhang L, Xu B, Dai J, Circulation., 119, 1776 (2009)
  22. Hu FQ, Wu XL, Du YZ, You J, Yuan H, Eur. J.Pharm. Biopharm., 69, 117 (2008)
  23. Lee CM, Jang D, Kim J, Cheong SJ, Kim EM, Jeong MH, Kim SH, Kim DW, Lim ST, Sohn MH, Jeong YY, Jeong HJ, Bioconjug. Chem., 22, 186 (2011)
  24. Zhang J, Chen XG, Peng WB, Liu CS, Nanomedicine., 4, 208 (2008)