The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model

作者：Guzeloglu Mehmet^*; Gul Mehmet; Reel Buket; Yurekli Ismail; Aykut Koray; Hazan Eyup

来源：Anadolu Kardiyoloji Dergisi-The Anatolian Journal of Cardiology, 2011, 11(2): 93-100.

DOI：10.5152/akd.2011.026

• Neointimal
• matrix metalloproteinases (MMPs)
• zoledronic acid
• rabbit

Objective: The aim of the present study was to investigate the effect of zoledronic acid (ZA), as a matrix metalloproteinase inhibitor, on neointimal hyperplasia in rabbit carotid anastomosis model.
Methods: New Zealand male rabbits were divided into two groups as placebo and treatment groups in this experimental study. After anesthesia, the right carotid artery of each rabbit was end-to-end anastomosed with an 8/0 polypropylene suture. Left carotid artery was kept as control without any operation. Placebo group (n=6) received phosphate buffered saline (PBS) (0.5mL/kg/day/s.c.) for 28 days postoperatively, whereas ZA group (n=6) received ZA (100 mu g/kg/day/s.c.) for the same period. After sacrification, the anastomosed and control arteries were isolated. Morphometric and immunohistochemical examinations were performed. Statistical analyses of morphometric and immunohistochemical data were performed using two-way ANOVA and Chi-square test respectively.
Results: In PBS group, vascular injury in the anastomosed artery significantly increased the intimal area (anastomosed: 112.51 +/- 61.18 mu m(2)*1000 vs. control: 22.62 +/- 4.26 mu m(2)*1000, p<0.01) and intima/media index (anastomosed: 0.347 +/- 0.29 vs. control: 0.075 +/- 0.01, p<0.05) compared to control artery. ZA significantly reduced the intimal area (39.29 +/- 18.21 mu m(2)*1000, p<0.01) and intima/media index (0.112 +/- 0.07, p<0.05) compared to PBS group. Additionally, a-smooth muscle actin immunopositivity was found significantly decreased in anastomosed arteries from ZA group (ZA: 2.33 +/- 0.52 vs. PBS: 3.50 +/- 0.5, p<0.05). Moreover, intensive gelatinase (MMP-2 and MMP-9) immunoreactivities were clearly seen in anastomosed arteries compared to control arteries from PBS group. ZA apparently decreased immunopositivities for gelatinases in anastomosed arteries.
Conclusion: ZA might be a promising agent for prevention of neointimal hyperplasia, which is the most significant cause of graft failures in late postoperative period. (Anadolu Kardiyol Derg 2011; 11: 93-100)

• 出版日期2011-3