[Effects of TIMP-2 gene transfer on atherosclerotic plaque in rabbits].
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.
Wang
Chang-qian
CQ
Department of Cadiology, Renji Hospital, Affiliated to Shanghai Second Medical University, Shanghai 200001, China.
Wang
Shun
S
Tang
Da-ming
DM
Lin
Xu
X
Ding
Hong-yi
HY
Xie
Xiu-lan
XL
Xu
Yi-min
YM
Wang
Bin-yao
BY
Huang
Ding-jiu
DJ
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
D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen