title: The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model.
abstract: 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 µg/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 µm(2)*1000 vs. control: 22.62±4.26 µm(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 µm(2)*1000 , p<0.01) and intima/media index (0.112±0.07, p<0.05) compared to PBS group. Additionally, α-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.
  
  
  CONCLUSIONS
  ZA might be a promising agent for prevention of neointimal hyperplasia, which is the most significant cause of graft failures in late postoperative period.
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey. mehmetguzeloglu@hotmail.com
authors.forename: Mehmet
authors.initials: M
authors.lastname: Güzeloğlu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gül
authors.forename: Buket
authors.initials: B
authors.lastname: Reel
authors.forename: Ismail
authors.initials: I
authors.lastname: Yürekli
authors.forename: Koray
authors.initials: K
authors.lastname: Aykut
authors.forename: Eyüp
authors.initials: E
authors.lastname: Hazan
mesh_terms: D000199:Actins / Q000032:analysis; D000714:Anastomosis, Surgical; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology / Q000601:surgery*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000188:drug therapy / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D058426:Neointima / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D011897:Random Allocation; D000077211:Zoledronic Acid
chemical_list: D000199:Actins; D004164:Diphosphonates; D007093:Imidazoles; D061965:Matrix Metalloproteinase Inhibitors; D000077211:Zoledronic Acid; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9