title: Establishing an animal model of unstable atherosclerotic plaques.
abstract: BACKGROUND
  Atherosclerotic plaque rupture and coronary thrombosis are the main causes of acute coronary syndromes. However, there is no animal model of unstable atherosclerotic plaques. The presence of the p53 gene in advanced atherosclerotic plaques and the sensitivity to p53-induced apoptosis of smooth muscle cells isolated from these plaques prompted us to build an animal model of unstable atherosclerotic plaques using p53 gene transfer.
  
  
  METHODS
  Sixty-four New Zealand white rabbits were randomly divided into two groups: group A (n=54) and group B (n=10). Rabbits in group A underwent balloon-induced abdominal aortic wall injury and were then given a diet of 1% cholesterol, while rabbits in group B were given a diet of 1% cholesterol without the induction of aortic wall injury. At the end of the eighth week, rabbits in group A were randomly divided into two subgroups: group A1 (n=27) and group A2 (n=27). Recombinant adenovirus carrying p53 or beta-galactosidase (LacZ) genes were injected through a catheter into the aortic segments rich in plaques in groups A1 and A2, respectively. Two weeks later, 10 rabbits each from groups A1 and A2 were killed to observe the occurrence of spontaneous plaque ruptures, and the remaining rabbits in groups A1, A2, and B all underwent pharmacological triggering with an injection of Chinese Russell's viper venom (CRVV) and histamine.
  
  
  RESULTS
  The over expression of p53 in group A1 [(32.4 +/- 10.2)% vs (15.8 +/- 3.6)% in group A2 and (16.2 +/- 6.7)% in group B, P < 0.001, respectively] resulted in a marked increase in cellular apoptosis [(2.5 +/- 0.8)% vs (1.0 +/- 0.3)% in group A2 and (0.9 +/- 0.4)% in group B, P < 0.01, respectively], an accumulation of inflammatory cells within the plaques, and a significant decrease in vascular smooth muscle cells (VSMCs) and in the thickness of the fibrous caps. Although spontaneous plaque rupture was rare in group A1, plaque ruptures and thrombosis occurred in 12 rabbits with a total of 20 lesions after pharmacological triggering. By contrast, pharmacological triggering led to plaque rupture and thrombosis in only 5 rabbits for a total of 7 lesions in group A2 and in none of the rabbits in group B.
  
  
  CONCLUSIONS
  After transfection with human wild-type p53 gene and pharmacological triggering, plaque rupture and thrombosis occur in most atherosclerotic lesions in rabbits, thus offering a reliable model for the further study of unstable atherosclerotic plaques.
authors.affiliation: Department of Cardiology, Qilu Hospital, Shandong University, Ji'nan 250012, China.
authors.forename: Wen-qiang
authors.initials: WQ
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Ji
authors.forename: Yue
authors.initials: Y
authors.lastname: Yin
authors.forename: Yong-feng
authors.initials: YF
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008297:Male; D008854:Microscopy, Electron; D011817:Rabbits; D013927:Thrombosis / Q000209:etiology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D008055:Lipids; D016159:Tumor Suppressor Protein p53