Background

Ultrasound molecular imaging was used to evaluate the therapeutic effects of antioxidant therapy with EUK-207, which has superoxide dismutase and catalase activities, on suppressing high-risk atherosclerotic features.

Methods

Mice with age-dependent atherosclerosis produced by deletion of the low-density lipoprotein receptor and Apobec-1 were studied at 20 and 40 weeks of age. EUK-207 or vehicle was administered for the preceding 8 weeks. Therapy for 28 weeks was also studied for 40-week-old mice. Ultrasound molecular imaging of the thoracic aorta was performed with contrast agents targeted to endothelial P-selectin, von Willebrand factor A1-domain, and platelet glycoprotein Ibα or control agent. Aortic plaque area and macrophage content were assessed by histology.

Results

In 20-week-old double-knockout mice, EUK-207 compared with sham therapy produced only nonsignificant trends for reduction in molecular imaging signal for endothelial P-selectin, von Willebrand factor A1-domain, and platelet adhesion. At 40 weeks, EUK-207 given for 8 or 28 weeks significantly (P < .05) reduced signal for all three endothelial-associated events essentially to background levels, with the exception of glycoprotein Ibα signal after 8 weeks (P = .06). On aortic histology, EUK-207 therapy for 8 weeks did not affect plaque area or macrophage content at either age. However, EUK-207 for 28 weeks almost completely suppressed plaque development (350 ± 258 vs 4 ± 6 × 10³ μm², P = .014) and macrophage content (136 ± 103 vs 3 ± 2 × 10³ μm², P = .002) compared with control mice at 40 weeks.

Conclusions

Molecular imaging can be used to assess vascular responses to antioxidants and has demonstrated that certain antioxidants reduce vascular endothelial activation and platelet adhesion, but reductions in plaque size and macrophage content occurs only with long-duration therapy that is started early.

中文翻译：

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通过对比超声分子成像评估动脉粥样硬化的新型抗氧化疗法

 背景

超声分子成像用于评估 EUK-207 抗氧化疗法在抑制高危动脉粥样硬化特征方面的治疗效果，EUK-207 具有超氧化物歧化酶和过氧化氢酶活性。

 方法

研究人员在 20 周龄和 40 周龄时对患有因低密度脂蛋白受体和 Apobec-1 缺失而产生的年龄依赖性动脉粥样硬化的小鼠进行了研究。之前 8 周施用 EUK-207 或媒介物。还对 40 周龄小鼠进行了 28 周的治疗研究。使用针对内皮 P-选择素、冯维勒布兰德因子 A1 结构域和血小板糖蛋白 Ibα 的造影剂或对照剂进行胸主动脉超声分子成像。通过组织学评估主动脉斑块面积和巨噬细胞含量。

 结果

在 20 周大的双敲除小鼠中，与假治疗相比，EUK-207 仅产生内皮 P-选择素、血管性血友病因子 A1 结构域和血小板粘附的分子成像信号减少的非显着趋势。 40 周时，给予 EUK-207 8 或 28 周显着 ( P < .05) 将所有三种内皮相关事件的信号基本上降低至背景水平，但 8 周后糖蛋白 Ibα 信号除外 ( P = .06) 。在主动脉组织学上，EUK-207 治疗 8 周并未影响任一年龄的斑块面积或巨噬细胞含量。然而，EUK-207 持续 28 周几乎完全抑制了斑块形成（350 ± 258 vs 4 ± 6 × 10 ³ μm ² ， P = .014）和巨噬细胞含量（136 ± 103 vs 3 ± 2 × 10 ³ μm ² ， P） = .002) 与 40 周时的对照小鼠相比。

 结论

分子成像可用于评估血管对抗氧化剂的反应，并已证明某些抗氧化剂可减少血管内皮活化和血小板粘附，但斑块大小和巨噬细胞含量的减少仅发生在早期开始的长期治疗中。