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Molecular Imaging Reveals Rapid Reduction of Endothelial Activation in Early Atherosclerosis With Apocynin Independent of Antioxidative Properties

Khanicheh, E. and Qi, Y. and Xie, A. and Mitterhuber, M. and Xu, L. and Mochizuki, M. and Daali, Y. and Jaquet, V. and Krause, K. H. and Ruggeri, Z. M. and Kuster, G. M. and Lindner, J. R. and 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, Vol. 33, H. 9. pp. 2187-2192.

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Official URL: http://edoc.unibas.ch/dok/A6183992

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Abstract

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.; 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Myocardial Research (Kuster Pfister)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cardiovascular Molecular Imaging (Kaufmann)
UniBasel Contributors:Kaufmann, Beat and Kuster Pfister, Gabriela
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Heart Association
ISSN:1079-5642
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:12
Deposited On:06 Dec 2013 09:36

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