Effects of human tissue kallikrein 1 gene delivery on carotid artery neointima formation after balloon angioplasty in spontaneously hypertensive rats
10.3760/cma.j.issn.0253-3758.2010.01.018
- VernacularTitle:人组织激肽释放酶基因转移对球囊拉伤后大鼠颈总动脉内膜的影响
- Author:
Hui-Zhen YU
1
;
Liang-Di XIE
;
Peng-Li ZHU
;
Chang-Sheng XU
;
Hua-Jun WANG
;
Ti-Yuan LI
Author Information
1. 福建医科大学省立临床医学院
- Keywords:
Tunica intima;
Gene transfer,horizontal;
Tissue kallikreins
- From:
Chinese Journal of Cardiology
2010;38(1):67-71
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of human tissue kallikrein 1 (Ad-hKLK1) gene delivery on the neointima formation in carotid arteries of spontaneously hypertensive rats (SHRs). Methods Carotid artery restenosis was induced in male SHR rats by balloon-injury. Rats were randomly assigned into 4 groups: Sham-operated (n = 6); Angioplasty (phosphate buffered solution 50 μl, n = 8); Vector virus (control virus, 1×10~9 IU in 50 μl, n =8) and Ad-hKLK1 (Ad-hKLK1, 1×10~9 IU in 50 μl, n =8). Rats were sacrificed 4 weeks later. The wall-to-lumen area ratio and intima/media ratio in carotid artery were assessed by image analysis in HE stained sections. The mRNA bradykinin receptor(B1R and B2R) expressions were detected by RT-PCR. The protein expression of the cycle-independent kinase inhibitors p27Kip1 and p21Cip1 were determined by Western blot analysis. Results Wall-to-lumen area ratio reduced 35.6% and intima/media ratio reduced 38.8% in Ad-hKLK1 treated SHRs compared to angioplasty group (all P <0.001). The expression of p27Kip1 and p21Cip1 increased significantly in Ad-hKLK1 treated SHRs compared with angioplasty rats (all P <0.001). The mRNA expression of B2R was significantly upregulated in angioplasty rats compared with sham-operated rats (P <0.05) while mRNA expression of B1R was similar between the 2 groups. Conclusion hKLK1 gene delivery may effectively reduce neointimal formation via downregulating bradykinin B2R and up-regulating the expressions of p27Kip1, p21Cip1 signaling pathways in carotid arteries of SHRs after balloon injury.
