[Effects of human tissue kallikrein 1 gene delivery on carotid artery neointima formation after balloon angioplasty in spontaneously hypertensive rats].
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 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.


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 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.


CONCLUSIONS
hKLK1 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.
Yu
Hui-zhen
HZ
Hypertension Institution Research of Fujian, First Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China.
Xie
Liang-di
LD
Zhu
Peng-li
PL
Xu
Chang-sheng
CS
Wang
Hua-jun
HJ
Li
Ti-yuan
TY
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D017536:Carotid Artery, Common / Q000473:pathology*; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D058426:Neointima / Q000209:etiology*; D051381:Rats; D011918:Rats, Inbred SHR; D020840:Tissue Kallikreins / Q000235:genetics*
D020840:Tissue Kallikreins