[The beneficial effect of phVEGF165 transfer on vascular remodelling after balloon injury and its possible mechanisms].
OBJECTIVE
To investigate the effect of phVEGF165 transfer on vascular remodelling after balloon injury and its possible mechanisms.


METHODS
90 New Zealand white rabbits were divided randomly into 3 groups: group I (balloon injury group), group II (pAdtrackCMV group) and group III (pAdtrackCMV-VEGF165 group). All animals were given hypercholesterol diet for 7 days before experiment and continued to receive hypercholesterol diet until being killed. Each group was further divided into five subgroups according to the sacrifice time (3 days, 1, 2, 4 and 8 weeks after transfection). Blood samples and arteries were harvested for further analysis.


RESULTS
At the end of 2 weeks, areas of neointima plus media of group III were smaller than those of group I and II (P < 0.05). The areas under external elastic membrane were larger in group III at 4 weeks and lumen stenosis rates were significantly lower than group I and II (P < 0.05 or 0.01). In group III, VEGF165, metalloproteinases (MMPs) -1, -2, -9 and their tissue inhibitors (TIMPs) 1, 2 could be detected from 3 days after gene transfer and reached the highest level at 2 weeks time and could not be detected by 8 weeks time. In groups I and II, MMP-2 and TIMP-1, -2 could be detected during the whole procedure and the value of TIMP1/MMP1 was significantly higher than in group III (P < 0.01).


CONCLUSIONS
Remodelling is the main reason for restenosis (RS) after vascular balloon injury. Local pAdtrackCMV-VEGF165 transfer can specifically change the expression of MMPs and facilitate the positive remodelling process, hence, inhibiting restenosis.
Wei
Fang
F
Department of Cardiology, Guangdong Provincial People's Hospital, Guangzhou 510100, China.
Geng
Qingshan
Q
Zhang
Bin
B
Feng
Jianzhang
J
Lin
Huahuan
H
Jiang
Zuxun
Z
Yu
Xiyong
X
Zhou
Gang
G
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D023903:Coronary Restenosis / Q000209:etiology* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020782:Matrix Metalloproteinases