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.

Angioplasty, Balloon ; adverse effects ; Animals ; Carotid Artery, Common ; pathology ; Gene Transfer Techniques ; Humans ; Male ; Neointima ; etiology ; Rats ; Rats, Inbred SHR ; Tissue Kallikreins ; genetics

We investigated tissue responses to endoskeleton stent grafts for saccular abdominal aortic aneurysms (AAAs) in canines. Saccular AAAs were made with Dacron patch in 8 dogs, and were excluded by endoskeleton stent grafts composed of nitinol stent and expanded polytetrafluoroethylene graft. Animals were sacrificed at 2 months (Group 1; n = 3) or 6 months (Group 2; n = 5) after the placement, respectively. The aortas embedding stent grafts were excised en bloc for gross inspection and sliced at 5 to 8 mm intervals for histopathologic evaluation. Stent grafts were patent in all except a dog showing a thrombotic occlusion in Group 2. In the 7 dogs with patent lumen, the graft overhanging the saccular aneurysm was covered by thick or thin thrombi with no endothelial layer, and the graft over the aortic wall was completely covered by neointima with an endothelial layer. Transgraft cell migration was less active at an aneurysm than at adjacent normal aorta. In conclusion, endoskeleton stent grafts over saccular aneurysms show no endothelial coverage and poor transgraft cell migration in a canine model.
Alloys/chemistry ; Angiography ; Animals ; Aortic Aneurysm, Abdominal/*pathology/surgery/ultrasonography ; Cell Movement ; Disease Models, Animal ; Dogs ; Endothelial Cells/cytology ; Neointima/etiology ; Polytetrafluoroethylene/chemistry ; *Stents ; Thrombosis/etiology ; Tomography, X-Ray Computed