RING finger protein 10 prevents neointimal hyperplasia by promoting apoptosis in vitro and in vivo

Aims Vascular restenosis and neointimal hyperplasia are enhanced in metabolic syndrome (MetS). Vascular smooth muscle cell (VSMC) proliferation is a key step during restenosis and is suppressed by RING finger protein 10 (RNF10). However, the effect of RNF10 on neointimal hyperplasia is unknown. In the present study, we explored whether RNF10 over-expression prevents neointimal hyperplasia in a MetS rat model and in cultured VSMCs exposed to high glucose. Main methods An adenovirus encoding RNF10 (Ad-RNF10) or control green fluorescent protein (Ad-GFP) was delivered to balloon-injured carotid arteries in MetS rats and cultured rat VSMCs exposed to high glucose. Neointimal hyperplasia was measured, and the apoptosis index in the neointima was evaluated. The protein levels of RNF10, caspase-3, Bcl-2 and Bax in the injured vessels and VSMCs were determined. Key findings Ad-RNF10 prevented the development of neointimal hyperplasia in balloon-injured vessels. Furthermore, an increase in the apoptosis index and cleaved caspase-3 protein expression and a decrease in Bcl-2 expression were detected in the injured vessels after Ad-RNF10 treatment. Meanwhile, increased caspase-3 protein expression and decreased Bcl-2 expression were detected in VSMCs treated with Ad-RNF10. Significance RNF10 over-expression strongly suppresses neointimal hyperplasia via increased apoptosis, constituting a promising new therapeutic target for vascular restenosis.