title: [Effects of TIMP-2 gene transfer on atherosclerotic plaque in rabbits].
abstract: OBJECTIVE
  To evaluate the effects of TIMP-2 local gene transfer on atherosclerotic plaque.
  
  
  METHODS
  Atherosclerosis models were induced by denuding femoral artery endothelium plus high lipid diet in rabbits. TIMP-2 gene was transferred locally by balloons eluted with pcDNA3-TIMP-2. RT-PCR and Western blot were performed to verify exogenous genes transfer. MMPs activity in atherosclerotic plaque was evaluated by zymography. HE and VG staining and automatic image analysis system were used for pathological analysis of atherosclerotic femoral arteries. The lumen area of the vessel and the collagen contents in the atherosclerotic plaque were measured.
  
  
  RESULTS
  The expression of TIMP-2 gene in pcDNA3-TIMP-2 transferred group was significantly higher than control-vector transferred group at the end of week 2 after operation and reached the peak at the end of week 4. Comparing with the control group, the expression of TIMP-2 protein in treated group was also higher at the end of week 2, 4, and 8 after operation. Correspondingly, the MMP-2 and MMP-9 activities were lower in treated group. The thickness of fibrous cap of atherosclerotic plaque and the amount of collagen of the lesion were increased significantly in treated group compared with the control group, but there were no significant differences in vessel lumen area.
  
  
  CONCLUSIONS
  TIMP-2 gene transfer locally in atherosclerotic plaque could inhibit the activities of MMP-2 and MMP-9 in the lesion, increase the thickness of fibrous cap and the amount of collagen of the lesion, but may have no effect on the degree of the stenosis.
authors.affiliation: Department of Cadiology, Renji Hospital, Affiliated to Shanghai Second Medical University, Shanghai 200001, China.
authors.forename: Chang-qian
authors.initials: CQ
authors.lastname: Wang
authors.forename: Shun
authors.initials: S
authors.lastname: Wang
authors.forename: Da-ming
authors.initials: DM
authors.lastname: Tang
authors.forename: Xu
authors.initials: X
authors.lastname: Lin
authors.forename: Hong-yi
authors.initials: HY
authors.lastname: Ding
authors.forename: Xiu-lan
authors.initials: XL
authors.lastname: Xie
authors.forename: Yi-min
authors.initials: YM
authors.lastname: Xu
authors.forename: Bin-yao
authors.initials: BY
authors.lastname: Wang
authors.forename: Ding-jiu
authors.initials: DJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology; D015153:Blotting, Western; D003094:Collagen / Q000032:analysis; D022761:Gene Transfer, Horizontal; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics* / Q000502:physiology
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen