MicroRNA-221 sponge therapy attenuates neointimal hyperplasia and improves blood flows in vein grafts
| Autor: | Chun Huang, Kai-Chuen Lee, Xiao-Wen Wang, Zhi-Qian Lu, Bo Feng, Xiao-Yong Xiang, Rui Zhou, Jiabiao Hu, Xiangjun He |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Neointima medicine.medical_specialty Vascular smooth muscle Genetic enhancement 030204 cardiovascular system & hematology medicine.disease_cause Muscle Smooth Vascular Adenoviridae Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine In vivo medicine Animals Cells Cultured Neointimal hyperplasia Hyperplasia business.industry Genetic Therapy medicine.disease Rats Surgery MicroRNAs 030104 developmental biology Cancer research Vascular Grafting Jugular Veins Cardiology and Cardiovascular Medicine business Vein graft disease Blood Flow Velocity |
| Zdroj: | International Journal of Cardiology. 208:79-86 |
| ISSN: | 0167-5273 |
| DOI: | 10.1016/j.ijcard.2016.01.006 |
| Popis: | Vein graft failure due to neointimal hyperplasia remains an important and unresolved problem of cardiovascular surgery. MicroRNA-221 (miR-221) has been shown to play a major role in regulating vascular smooth muscle cell (VSMC) proliferation and phenotype transformation. Thus, the purpose of this study is to determine whether adenovirus mediated miR-221 sponge gene therapy could inhibit vein graft neointimal hyperplasia.Adenovirus encoding miR-221 sponge (Ad-miR-221-SP) was used to inhibit VSMC proliferation in vitro and neointimal formation in vivo. Expression of miRNA-221 was evaluated in cultured VSMC and in rat vein graft models following transduction with Ad-miR-221-SP, Ad-Control-SP (without miR-221 antisense binding sites), or Ad-GFP (control). To accelerate the transfer of miR-221 sponge gene to the vein grafts, 20% poloxamer F-127 gel was used to extend virus contact time and 0.25% trypsin to increase virus penetration.miR-221 sponges can significantly decrease the expression of miR-221 and proliferation in cultured VSMC. Cellular proliferation rates were significantly reduced in miR-221 sponge treated grafts as compared with controls at 6 weeks after bypass surgery (19.8% versus 43.6%, P=0.0028). miR-221 sponge gene transfer reduced the neointimal area (210.75 ± 24.13 versus 67.01 ± 12.02, P0.0001), neointimal thickness (171.86 ± 27.87 versus 64.13 ± 16.23, P0.0001) and neointima/media ratio (0.74 ± 0.21 versus 1.95 ± 0.25, P0.0001) in vein grafts versus controls. miR-21 sponge treatment was also improved hemodynamics in vein grafts. We have further identified that p27 (Kip1) is a potential target gene of miR-221 in vein grafts.miR-221 sponge therapy can significantly reduce miR-221 activity and inhibit neointimal hyperplasia in vein grafts. Locally adventitial delivery of adenoviruses mediated miRNA sponges may be promising gene therapies to prevent vein graft failure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect