Department of Cardiovascular Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vascular Diseases, Beijing, China.
Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vascular Diseases, Beijing, China.
Biomed Pharmacother. 2023 Sep;165:115262. doi: 10.1016/j.biopha.2023.115262. Epub 2023 Aug 3.
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.
血管介入治疗后，新生内膜增生仍然是一个障碍。叉头框转录因子 O1（FoxO1）是一种具有独特叉头结构域的转录因子，间接参与多种生理过程。FoxO1 的表达和信号转导也影响血管平滑肌细胞的能量代谢，可能影响新生内膜增生。我们的假设是 FoxO1 抑制大鼠血管成形术模型中的新生内膜增生。在大鼠主动脉补片血管成形术模型中比较了四组：未治疗的对照组、PLGA 基质中包被 AS184286（FoxO1 抑制剂）的补片、PLGA 基质中包被 FoxO1 的补片和 PLGA 基质中包被 MLN0905（PLK1 抑制剂）的补片。第 14 天采集补片并进行分析。补片血管成形术后观察到 FoxO1 阳性和 p-FoxO1 细胞。通过在 PLGA 基质中包被外源性 FoxO1 蛋白的补片添加 FoxO1，显著抑制新生内膜厚度（p=0.0012）。处理组的 CD3（p=0.0003）、CD45（p<0.0001）和 PCNA（p<0.0001）阳性细胞数量明显减少。PLK1 是 FoxO1 的上游转录调节因子，调节 FoxO1 的表达和功能。MLN0905 PLGA 包被的补片表现出相似的新生内膜厚度和炎症细胞积聚减少。FoxO1 是抑制新生内膜增生的一种有前途的治疗策略。
