Neointimal hyperplasia in the vessel grafts transfected with endothelial nitric oxide synthase
- VernacularTitle:内皮型一氧化氮合酶基因转染对移植人工血管内膜增生的作用
- Author:
Fei PEI
;
Junyan LI
;
Li ZHANG
;
Rui HE
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2008;12(40):7975-7979
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Smooth muscle cells (SMCs) proliferation and transmigration and platelet activation cause thrombogenesis and lead to grafted vessel restenosis. Nitric oxide (NO) can inhibit the above-mentioned biological responses, but whether endothelial nitric oxide synthase (eNOS) gene transfection can inhibit the neointimal hyperplasia in graft seeded with SMCs remains uncertain.OBJECTIVE: This study was designed to further investigate the effect of eNOS gene transfection on neointimal hyperplasia in the grafts seeded with SMCs.DESIGN, TIME AND SETTING: This study, a repeated observation and measurement experiment, was performed at the Central Laboratory and Laboratory of Molecular Biology of Xi'an Jiaotong University Medical College from April 2006 to May 2007.MATERIALS: One 1-month-old New Zealand rabbit was used to acquire SMCs. Another 18 adult New Zealand rabbits were randomly divided into 3 groups (n=6).In normal control group,the vessel graft with no SMCs were transplanted; In SMC/lacZ group, the vessel grafts with SMCs transfected with lacZ were transplanted;In SMC/eNOS group,the vessel grafts with SMCs seeded with eNOS were transplanted.METHODS: Rabbit SMCs were transduced with pseudotyped retroviral vectors, Murine leukemia virus/vesicular stomatitis virus G glycoprotein, carrying genes coding for eNOS or lacZ gene. The SMCs then were seeded on the vessel grafts and implanted into the rabbit abdominal aorta using vessel bypass transplantation.MAIN OUTCOME MEASURES: Nitric oxide (NO) content in the supernatant of cells transfected with eNOS and lacZ gene was detected by citrulline method. The grafts were stained with X-gal to visualize the seeded cells: the seeded SMCs were stained blue,while eNOS were stained red. The thickness of the neointima on a graft was measured with a microscope.RESULTS: Eighteen rabbits were all included in the final analysis. NO content in the SMC/eNOS group was significantly higher than that in the normal control group (P<0.05). The SMCs transfected with lacZ gene showed blue after X-gal staining under the inverted microscope. Thirty days after implantation, there was no difference in neointimal thickness between normal grafts and grafts seeded with eNOS or lacZ transduced SMCs (P>0.05).100 days after implantation,the neointimal thickness on grafts seeded with eNOS transduced SMCs was similar to that of unseeded grafts (P>0.05 ), but was significantly thinner than that on grafts seeded with SMCs transduced with only lacZ gene (P<0.05).CONCLUSION: eNOS gene transfection inhibits nenintimal hyperplasia in the vessel graft seeded with SMCs.
