Division of Cardiology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2187-92. doi: 10.1161/ATVBAHA.113.301710. Epub 2013 Aug 1.
Antioxidative drugs continue to be developed for the treatment of atherosclerosis. Apocynin is an nicotinamide adenine dinucleotide phosphate oxidase inhibitor with anti-inflammatory properties. We used contrast-enhanced ultrasound molecular imaging to assess whether short-term apocynin therapy in atherosclerosis reduces vascular oxidative stress and endothelial activation
Genetically modified mice with early atherosclerosis were studied at baseline and after 7 days of therapy with apocynin (4 mg/kg per day IP) or saline. Contrast-enhanced ultrasound molecular imaging of the aorta was performed with microbubbles targeted to vascular cell adhesion molecule 1 (VCAM-1; MB(V)), to platelet glycoprotein Ibα (MB(Pl)), and control microbubbles (MB(Ctr)). Aortic vascular cell adhesion molecule 1 was measured using Western blot. Aortic reactive oxygen species generation was measured using a lucigenin assay. Hydroethidine oxidation was used to assess aortic superoxide generation. Baseline signal for MBV (1.3 ± 0.3 AU) and MB(Pl )(1.5 ± 0.5 AU) was higher than for MBCtr (0.5 ± 0.2 AU; P<0.01). In saline-treated animals, signal did not significantly change for any microbubble agent, whereas short-term apocynin significantly (P<0.05) reduced vascular cell adhesion molecule 1 and platelet signal (MBV: 0.3 ± 0.1; MBPl: 0.4 ± 0.1; MBCtr: 0.3 ± 0.2 AU; P=0.6 between agents). Apocynin reduced aortic vascular cell adhesion molecule 1 expression by 50% (P<0.05). However, apocynin therapy did not reduce reactive oxygen species content, superoxide generation, or macrophage content.
Short-term treatment with apocynin in atherosclerosis reduces endothelial cell adhesion molecule expression. This change in endothelial phenotype can be detected by molecular imaging before any measurable decrease in macrophage content and is not associated with a detectable change in oxidative burden.
抗氧化药物继续被开发用于治疗动脉粥样硬化。阿朴肉桂酸是一种烟酰胺腺嘌呤二核苷酸磷酸氧化酶抑制剂，具有抗炎作用。我们使用对比增强超声分子成像来评估短期阿朴肉桂酸治疗动脉粥样硬化是否会降低血管氧化应激和内皮细胞激活。
在基础状态和用阿朴肉桂酸（每天 4 毫克/千克腹腔内注射）或盐水治疗 7 天后，对早期动脉粥样硬化的基因修饰小鼠进行了研究。使用靶向血管细胞黏附分子 1（VCAM-1；MB(V)）、血小板糖蛋白 Ibα（MB(Pl)）和对照微泡（MB(Ctr)）的微泡进行主动脉对比增强超声分子成像。使用 Western blot 测量主动脉血管细胞黏附分子 1。使用荧光素酶测定法测量主动脉活性氧生成。使用羟乙基二氢二嗪氧化来评估主动脉超氧化物生成。MB(V)（1.3±0.3 AU）和 MB(Pl)（1.5±0.5 AU）的基线信号高于 MB(Ctr)（0.5±0.2 AU；P<0.01）。在盐水处理的动物中，任何微泡剂的信号均无明显变化，而短期阿朴肉桂酸可显著（P<0.05）降低血管细胞黏附分子 1 和血小板信号（MB(V)：0.3±0.1；MB(Pl)：0.4±0.1；MB(Ctr)：0.3±0.2 AU；P=0.6 之间的代理）。阿朴肉桂酸使主动脉血管细胞黏附分子 1 的表达降低了 50%（P<0.05）。然而，阿朴肉桂酸治疗并未降低活性氧含量、超氧化物生成或巨噬细胞含量。
动脉粥样硬化中短期阿朴肉桂酸治疗可降低内皮细胞黏附分子的表达。这种内皮表型的变化可以通过分子成像检测到，而在巨噬细胞含量发生任何可测量的变化之前，并且与氧化应激负担的可检测变化无关。
