PloS one, 2015-03, Vol.10 (3), p.e0118826-e0118826
2015
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- Autor(en) / Beteiligte
- Titel
- Targeted inhibitory effect of Lenti-SM22alpha-p27-EGFP recombinant lentiviral vectors on proliferation of vascular smooth muscle cells without compromising re-endothelialization in a rat carotid artery balloon injury model
- Ist Teil von
- PloS one, 2015-03, Vol.10 (3), p.e0118826-e0118826
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- In-stent restenosis remains a serious problem after the implantation of drug-eluting stents, which is attributable to neointima formation and re-endothelialization. Here, we tried to find a new method which aims at selectively inhibiting proliferation of vascular smooth muscle cells (VSMC) proliferation without inhibition of re-endothelialization. We used the smooth muscle-specific SM22alpha promoter in a recombinant lentiviral vector to drive overexpression of cell-cycle inhibitor, p27, in VSMCs. p27 effectively inhibited VSMC proliferation mediated by cell cycle arrest at the G0/G1 checkpoint. The SM22alpha-p27 lentiviral vector inhibited VSMC proliferation more effectively than paclitaxel. Rats infected with Lenti-SM22alpha-p27 had a significantly lower intima/media (I/M) ratio and also showed inhibition of restenosis on day 28 after balloon injury. Moreover, the repair of injured endothelium, and re-endothelialization of the carotid artery wall, was not affected by the smooth muscle cell-specific expression of p27. A recombinant lentiviral vector carrying the SM22alpha promoter was used to effectively infect and selectively overexpress p27 protein in VSMCs, leading to inhibition of intimal hyperplasia without compromising endothelial repair.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0118826Titel-ID: cdi_plos_journals_1662426346
- Format
- –
- Schlagworte
- Adenoviruses, Angioplasty, Animals, Antineoplastic Agents, Phytogenic - pharmacology, Apoptosis, Balloon Occlusion, Balloon treatment, Biomedical materials, Cancer, Cardiovascular disease, Carotid Arteries - pathology, Carotid artery, Cell cycle, Cell division, Cell Proliferation, Cells, Cultured, Coronary vessels, Cyclin-Dependent Kinase Inhibitor p27 - biosynthesis, Cyclin-Dependent Kinase Inhibitor p27 - genetics, Cyclin-dependent kinases, Drug delivery, Endothelium, Endothelium, Vascular - physiopathology, G1 Phase Cell Cycle Checkpoints, Gene expression, Gene targeting, Genetic aspects, Genetic vectors, Green Fluorescent Proteins - biosynthesis, Green Fluorescent Proteins - genetics, Hospitals, Hyperplasia, Implantation, Implants, Inhibition, Injuries, Kinases, Lentivirus, Lentivirus - genetics, Male, Medicine, Methods, Microfilament Proteins - genetics, Muscle Proteins - genetics, Muscle, Smooth, Vascular - pathology, Muscles, Myocytes, Smooth Muscle - physiology, Neointima - metabolism, Neurology, Paclitaxel, Paclitaxel - pharmacology, Proteins, Rats, Rats, Wistar, Repair, Restenosis, Rodents, Science, Smooth muscle, Stents, Studies, Surgical implants, Vascular Remodeling, Wound Healing