Antisense MMP-9 oligonucleotide suppresses aneurysmal formation in vivo
| Project/Area Number |
12671160
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
ZEMPO Nobuya Yamaguchi University, School of Medicine, Associate Prof., 医学部, 助教授 (00206666)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ESATO Kensuke Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (10034943)
SEYAMA Atsushi Yamaguchi University, School of Medicine, Instructor, 医学部, 助手 (20333461)
TAKENAKA Hiroaki Yamaguchi University, Hospital, Instructor, 医学部・附属病院, 助手 (00314807)
FUJIOKA Kentarou Yamaguchi University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (80238542)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
|---|
| Keywords | aneurysm / antisense oligonucleotide / matrix metalloproteinase-9 / pluronic gel / pancreatic elastase / gene therapy / Matrix metalloproteinase-9 |
|---|
| Research Abstract |
The purpose of this experimental study was to explore the inhibitory effect of antisense matrix metallorpoteinase-9 (MMP-9) oligonucleotide on the suppression of aneurysmal formation in vivo. 0.5 ml (25 units/ml) of pancreatic elastase was infused into rat infrarenal abdominal aorta at 100 mmHg for 30 minutes. Mean diameter of the aorta was significantly increased after the elastase infusion (before; 1.276±0.119 mm, after; 2.143±0.145 mm, P<0.0001). Pluronic gel impregnated with antisense MMP-9 oligonucleotide (n=8) was applied on the exterior of elastase-infused aorta. Pluronic jel with randomized oligonucleotide (n=8) or pluronic gel alone (n=7) was also applied on the aorta as control. Rats were sacrificed 7 days after surgery, and diameter of the aorta was measured. Some aortas were put into liquid nitrogen for zymography and western blot analysis. Diameter of the aorta treated with antisense MMP-9 oligonucleotide was significantly less at 7 days compared with that received the randomized oligonucleotide or vehicle alone (antisense oligo; 5.362±1.948 mm, randomized oligo; 7.852±2.789 mm, pluronic jel; 7.524±2.074 mm, p<0.05). The increased ratio of diameter was also significantly less in the antisense oligonucleotide group than in the randomized oligonucleotide or vehicle (antisense oligo; 2.510±0.956, randomized oligo; 3.746±1.268, pluronic jel; 3.503±1.115, P<0.05). By using zymography and western blotting, we are now conducting MMP-9 protein assays for investigating whether antisense MMP-9 oligonucleotide inhibits MMP-9 activity in aorta and in cultured rat peritoneal macrophages. In conclusion, antisense MMP-9 oligonucleotide may promise a feasible treatment for inhibiting aortic aneurysm.
|
Report
(3 results)
Research Products
(12 results)
