Effects of human tissue kallikrein 1 gene delivery on carotid artery neointima formation after balloon angioplasty in spontaneously hypertensive rats.
- Author:
Hui-zhen YU
1
;
Liang-di XIE
;
Peng-li ZHU
;
Chang-sheng XU
;
Hua-jun WANG
;
Ti-yuan LI
Author Information
- Publication Type:Journal Article
- MeSH: Angioplasty, Balloon; adverse effects; Animals; Carotid Artery, Common; pathology; Gene Transfer Techniques; Humans; Male; Neointima; etiology; Rats; Rats, Inbred SHR; Tissue Kallikreins; genetics
- From: Chinese Journal of Cardiology 2010;38(1):67-71
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of human tissue kallikrein 1(Ad-hKLK1) gene delivery on the neointima formation in carotid arteries of spontaneously hypertensive rats (SHRs).
METHODSCarotid 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 microl, n = 8); Vector virus (control virus, 1 x 10(9) IU in 50 microl, n = 8) and Ad-hKLK1(Ad-hKLK1, 1 x 10(9) IU in 50 microl, 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 p2lCip1 were determined by Western blot analysis.
RESULTSWall-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 p2lCip1 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.
CONCLUSIONhKLK1 gene delivery may effectively reduce neointimal formation via downregulating bradykinin B2R and up-regulating the expressions of p27Kip1, p2lCip1 signaling pathways in carotid arteries of SHRs after balloon injury.