Molecular imaging reveals rapid reduction of endothelial activation in early atherosclerosis with apocynin independent of antioxidative properties

Elham Khanicheh, Yue Qi, Aris Xie, Martina Mitterhuber, Lifen Xu, Michika Mochizuki, Youssef Daali, Vincent Jaquet, Karl Heinz Krause, Zaverio M. Ruggeri, Gabriela M. Kuster, Jonathan R. Lindner, Beat A. Kaufmann

    Research output: Contribution to journalArticle

    31 Scopus citations

    Abstract

    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 Ibα (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.

    Original languageEnglish (US)
    Pages (from-to)2187-2192
    Number of pages6
    JournalArteriosclerosis, thrombosis, and vascular biology
    Volume33
    Issue number9
    DOIs
    StatePublished - Sep 2013

    Keywords

    • acetovanillone
    • atherosclerosis
    • microbubbles
    • molecular imaging
    • oxidative stress

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Fingerprint Dive into the research topics of 'Molecular imaging reveals rapid reduction of endothelial activation in early atherosclerosis with apocynin independent of antioxidative properties'. Together they form a unique fingerprint.

  • Cite this

    Khanicheh, E., Qi, Y., Xie, A., Mitterhuber, M., Xu, L., Mochizuki, M., Daali, Y., Jaquet, V., Krause, K. H., Ruggeri, Z. M., Kuster, G. M., Lindner, J. R., & Kaufmann, B. A. (2013). Molecular imaging reveals rapid reduction of endothelial activation in early atherosclerosis with apocynin independent of antioxidative properties. Arteriosclerosis, thrombosis, and vascular biology, 33(9), 2187-2192. https://doi.org/10.1161/ATVBAHA.113.301710