Co-overexpression of human tissue kallikrein 1 and human metalloproteinase 1 tissue inhibitor inhibits neointima formation in the rat artery after balloon angioplasty
10.3760/cma.j.issn.0253-3758.2016.05.014
- VernacularTitle:人组织激肽释放酶1和基质金属蛋白酶组织抑制物1基因共表达抑制大鼠颈动脉球囊拉伤后内膜增生
- Author:
Huizhen YU
1
;
Feng ZHANG
;
Pengli ZHU
;
Wei PAN
;
Shujie HUANG
;
Hong XIANG
Author Information
1. 福建省立医院干部特诊科福建医科大学省立临床医学院福建省临床老年病研究所
- Keywords:
Tunica intima;
Hyperplasia;
Tissue kallikreins;
Matrix metalloproteinases
- From:
Chinese Journal of Cardiology
2016;44(5):436-442
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of adenovirus-mediated human tissue kallikrein 1 (hTK-1) and/or human tissue metalloproteinase inhibitor 1 (hTIMP-1) gene delivery on the neointima formation in balloon-injured rat carotids and related mechanism.Methods Forty-six male Sprague-Dawley rats were randomly assigned into 6 groups with the random number table:(1) sham-operated group(n =6),(2) angioplasty group (n=8),(3) vector virus group (n=8),(4) hTK-1 group (n=8),(5) hTIMP-1 group (n =8),(6) hTK-1-hTIMP-1 group (n =8).Except sham rats,all rats underwent carotid artery balloon injury and local delivery of saline or different recombined adenoviruses respectively.Rats were sacrificed 14 days later.Intima/media area ratio was assessed on hematoxylin-eosin stained tissue section.Immunofluorescence images stained for hTK-1,hTIMP-1 were obtained and analyzed by the confocal microscope for co-localization examination of hTK-1 and hTIMP-1.The protein expression levels of hTK-1,hTIMP-1,matrix metalloproteinases (MMP)-2 and MMP-9 were determined by Western blot.Immune histochemical staining for PCNA was also performed.Results (1) Intima area,intima/media area ratio,PCNA,MMP-2 and MMP-9 levels were all significantly increased in rats underwent angioplasty (did or did not receive vector virus) compared with sham-operated rats (all P ＜ 0.01) while above parameters were similar between rats underwent angioplasty or vector virus delivery (all P ＞ 0.05).(2) The intima area of rats received vector virus,hTK-1,hTIMP-1 or dual gene transfer were (0.160 ± 0.010),(0.110 ± 0.015),(0.121 ± 0.016) or (0.081 ± 0.008) mm2 respectively,intima area was similar between rats received hTK-1 or hTIMP-1 (P ＞0.05),differences were found between other groups (all P ＜ 0.01).The intima/media area ratio of rats received vector virus,hTK-l,hTIMP-1 or dual gene transfer were 2.035 ± 0.117,1.443 ±0.097,1.522 ±0.078 or 0.972 ±0.072 respectively,no difference was found between rats received hTK-1 or hTIMP-1 in intima/media area ratio (all P ＞ 0.05),differences were found between other groups (all P ＜0.01).The MMP-2 and MMP-9 expression of rats received vector virus,hTK-1,hTIMP-1 or dual gene transfer were 0.817 ±0.036,0.606 ±0.044,0.571 ±0.061 or 0.455 ±0.030 and 0.745 ± 0.057,0.613 ±0.038,0.582 ±0.050 or0.473 ±0.038 respectively,no difference was found between rats received hTK-1 or hTIMP-1 in MMP-2 or MMP-9 expression (all P ＞0.05),differences were found between other groups (all P ＜0.01).The PCNA expression of rats received vector virus,hTK-1,hTIMP-1 or dual gene transfer were 0.065 ± 0.007,0.052 ± 0.004,0.055 ± 0.007 or 0.031 ± 0.004 respectively,no difference was found between rats received hTK-lor hTIMP-1 in PCNA expression (all P ＞ 0.05),differences were found between other groups (all P ＜ 0.01).Conclusion hTK-1 and hTIMP-1 co-overexpression may synergistically inhibit neointimal hyperplasia,attenuate vascular remodeling and reduce restenosis possibly via down regulating the expressions of PCNA,MMP-2 and MMP-9 in balloon-injured rat carotids.
