期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 33, 期 9, 页码 2187-2192出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.113.301710
关键词
acetovanillone; atherosclerosis; microbubbles; molecular imaging; oxidative stress
资金
- Swiss Clinicians Opting for Research (SCORE) grants from the Swiss National Science Foundation (SNSF) [SNSF 32323B_123819, 3232B0-141603, SNSF 144208]
- US National Institutes of Health [R01-DK-063508, R01-HL-078610, RC1-HL-100659, R01 HL42846]
- University Hospital Basel
- Swiss National Science Foundation (SNF) [3232B0-141603] Funding Source: Swiss National Science Foundation (SNF)
Objective-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 Approach and Results-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; MBV), to platelet glycoprotein Ib alpha (MBPl), and control microbubbles (MBCtr). 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 MBPl (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. Conclusions-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.
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