期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 13, 期 10, 页码 1309-1319出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.20254
关键词
MicroRNA; Neointimal formation; Gene therapy; Vein graft disease
资金
- Science and Technical Commission of Shanghai Municipality, China [15411952400]
- Key Program of Health Bureau of Chongqing, China [2013-1-015]
- Research Grants of The First Affiliated Hospital of Chongqing Medical University [PYJJ2017-11]
Background: Vein graft failure due to neointimal hyperplasia remains an important and unresolved complication of cardiovascular surgery. microRNA-21 (miR-21) plays a major role in regulating vascular smooth muscle cell (VSMC) proliferation and phenotype transformation. Thus, the purpose of this study was to determine whether adenovirus-mediated miR-21 sponge gene therapy was able to inhibit neointimal hyperplasia in rat vein grafts. Methods: Adenovirus-mediated miR-21 sponge was used to inhibit VSMC proliferation in vitro and neointimal formation in vivo. To improve efficiency of delivery gene transfer to the vein grafts, 20% poloxamer F-127 gel was used to increase virus contact time and 0.25% trypsin to increase virus penetration. Morphometric analyses and cellular proliferation were assessed for neointimal hyperplasia and VSMC proliferation. Results: miR-21 sponge can significantly decrease the expression of miR-21 and proliferation in cultured VSMCs. Cellular proliferation rates were significantly reduced in miR-21 sponge-treated grafts compared with controls at 28 days after bypass surgery (14.6 +/- 9.4 vs 34.9 +/- 10.8%, P= 0.0032). miR-21 sponge gene transfer therapy reduced the intimal/media area ratio in vein grafts compared with the controls (1.38 +/- 0.08 vs. 0.6 +/- 0.10, P< 0.0001). miR-21 sponge treatment also improved vein graft hemodynamics. We further identified that phosphatase and tensin homolog (PTEN) is a potential target gene that was involved in the miR-21-mediated effect on neointimal hyperplasia in vein grafts. Conclusions: Adenovirus-mediated miR-21 sponge gene therapy effectively reduced neointimal formation in vein grafts. These results suggest that there is potential for miR-21 sponge to be used to prevent vein graft failure.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据