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Inhibition of programmed death-1 decreases neointimal hyperplasia after patch angioplasty.
Journal of Biomedical Materials Research Part B: Applied Biomaterials ( IF 3.4 ) Pub Date : 2020-08-07 , DOI: 10.1002/jbm.b.34698
Hualong Bai 1, 2 , Zhiwei Wang 1 , Mingxing Li 1 , Peng Sun 1 , Shunbo Wei 1 , Wang Wang 2, 3 , Zhiju Wang 2, 3 , Ying Xing 2, 3 , Jingan Li 4 , Alan Dardik 5, 6
Affiliation  

Neointimal hyperplasia remains an obstacle after vascular interventions. Programmed death‐1 (PD‐1) antibody treatment decreases tumor cell proliferation and secretion of inflammatory factors, and several antineoplastic drugs show efficacy against neointimal hyperplasia. We hypothesized that inhibition of PD‐1 inhibits neointimal hyperplasia in a rat patch angioplasty model. In a rat aorta patch angioplasty model, four groups were compared: the control group without treatment, a single dose of humanized PD‐1 antibody (4 mg/kg) injected immediately after patch angioplasty, PD‐1 antibody‐coated patches, and BMS‐1 (PD‐1 inhibitor)‐coated patches. Patches were harvested (Day 14) and analyzed. After patch angioplasty, PD‐1‐positive cells were present. Inhibition of PD‐1 using both intraperitoneal injection of humanized PD1 antibody as well as using patches coated with humanized PD1 antibody significantly decreased neointimal thickness (p = 0.0199). There were significantly fewer PD‐1 (p = 0.0148), CD3 (p = 0.0072), CD68 (p = 0.0001), CD45 (p = 0.001), and PCNA (p < 0.0001)‐positive cells, and PCNA/α‐actin dual positive cells (p = 0.0005), in the treated groups. Patches coated with BMS‐1 showed similarly decreased neointimal thickness and accumulation of inflammatory cells. Inhibition of PD‐1 using PD‐1 antibody or its inhibitor BMS‐1 can significantly decrease neointimal thickness in vascular patches. Inhibition of the PD‐1 pathway may be a promising therapeutic strategy to inhibit neointimal hyperplasia.

中文翻译:

抑制程序性死亡-1 可减少补片血管成形术后的新内膜增生。

血管介入后,新生内膜增生仍然是一个障碍。程序性死亡-1 (PD-1) 抗体治疗可降低肿瘤细胞增殖和炎症因子的分泌,几种抗肿瘤药物显示出对抗新内膜增生的功效。我们假设在大鼠补片血管成形术模型中抑制 PD-1 会抑制新内膜增生。在大鼠主动脉贴片血管成形术模型中,比较了四组:未治疗的对照组、贴片血管成形术后立即注射单剂量人源化 PD-1 抗体(4 mg/kg)、PD-1 抗体涂层贴片和 BMS ‐1(PD-1 抑制剂)涂层贴剂。收获补丁(第 14 天)并进行分析。补片血管成形术后,存在 PD-1 阳性细胞。p = 0.0199)。PD-1 ( p = 0.0148)、CD3 ( p = 0.0072)、CD68 ( p = 0.0001)、CD45 ( p = 0.001) 和 PCNA ( p  < 0.0001) 阳性细胞和 PCNA/α-处理组中的肌动蛋白双阳性细胞 ( p = 0.0005)。涂有 BMS-1 的贴片表现出类似地减少了新内膜的厚度和炎症细胞的积聚。使用 PD-1 抗体或其抑制剂 BMS-1 抑制 PD-1 可显着降低血管斑块中的新内膜厚度。抑制 PD-1 通路可能是抑制新内膜增生的有希望的治疗策略。
更新日期:2020-08-07
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