FoxO1 is a negative regulator of neointimal hyperplasia in a rat model of patch angioplasty.

Neointimal hyperplasia persists as a barrier following vascular interventions. Forkhead Box O1 (FoxO1) is a transcription factor that possesses a distinctive fork head domain and indirectly contributes to various physiological processes. FoxO1 expression and signaling also impact the energy metabolism of vascular smooth muscle cells, potentially influencing neointimal hyperplasia. Our hypothesis is that FoxO1 inhibits neointimal hyperplasia in a rat patch angioplasty model. Four groups were compared in a rat aorta patch angioplasty model: the control group without treatment, patches coated with AS184286 (a FoxO1 inhibitor) in a PLGA matrix, patches coated with FoxO1 in a PLGA matrix, and patches coated with MLN0905 (a PLK1 inhibitor) in a PLGA matrix. The patches were harvested on Day 14 and subjected to analysis. FoxO1-positive and p-FoxO1 cells were observed after patch angioplasty. The addition of FoxO1 through patches coated with exogenous FoxO1 protein in a PLGA matrix significantly inhibited neointimal thickness (p = 0.0012). The treated groups exhibited significantly lower numbers of CD3 (p = 0.0003), CD45 (p < 0.0001), and PCNA (p < 0.0001)-positive cells. PLK1 is an upstream transcriptional regulator of FoxO1, governing the expression and function of FoxO1. MLN0905 PLGA-coated patches exhibited comparable reductions in neointimal thickness and inflammatory cell accumulation. FoxO1 represents a promising therapeutic strategy for inhibiting neointimal hyperplasia.