AI Article Synopsis
- * In lab experiments, VSMCs that overexpressed TP had increased levels of heme oxygenase (HO)-1, which was linked to higher amounts of the cell cycle inhibitor p27(KIP1) and a halt in cell division at the G1 phase.
- * In live rat studies, introducing TP significantly decreased VSMC migration and neointima formation after vascular injury, indicating that targeting TP could be a potential strategy for treating vascular obstructive diseases.
Article Abstract
Objective: Thymidine phosphorylase (TP) reportedly promotes endothelial cell migration and induces heme oxygenase (HO)-1 expression. However, its effect on vascular smooth muscle cells (VSMCs) is poorly understood. In this study, we examined the effect of TP on VSMCs in vitro and in vivo.
Methods And Results: Phagemid vector encoding human TP gene was transfected into rat VSMCs, and a clone overexpressing TP was selected (C2). C2 showed a slower migration and proliferation than VSMCs cloned with empty vector (pC) under basal, serum-stimulated, and hypoxic conditions. This decrease in proliferation correlated with TP-induced HO-1 expression and was reversed by inhibitors of either TP or HO activity. Furthermore, in C2, the cyclin-dependent kinase inhibitor (p27KIP1) was much more abundant than in pC, and the cell cycle was arrested at the G1 phase. TP or HO activity inhibitors decreased p27(KIP1) expression in C2 to the level seen in pC. Adventitial TP gene delivery significantly reduced neointimal VSMC migration and neointima formation in balloon-injured rat carotid arteries.
Conclusions: TP overexpression upregulated HO-1 expression and consequently increased p27(KIP1) in cultured VSMCs, and inhibited VSMC migration and proliferation in vitro and in vivo. TP represents a promising target for treating vascular obstructive disease.
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| http://dx.doi.org/10.1161/01.ATV.0000168914.85107.64 | DOI Listing |
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