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Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis

Khanicheh, Elham and Mitterhuber, Martina and Xu, Lifen and Haeuselmann, Stéphanie P. and Kuster, Gabriela M. and Kaufmann, Beat A.. (2013) Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis. PLoS ONE, Vol. 8, H. 3 , e58761.

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Official URL: http://edoc.unibas.ch/dok/A6183993

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Abstract

Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) with contrast enhanced ultrasound (CEU) could assess treatment effects on endothelial phenotype in early atherosclerosis.; Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day). At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM)) and control microbubbles (MB(Ctr)). Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression.; Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM) in non-treated animals (MB(VCAM) 2±0.3 vs MB(Ctr) 0.7±0.2, p>0.01), but not in statin-treated animals (MB(VCAM) 0.8±0.2 vs MB(Ctr) 1.0±0.2, p = ns; p>0.01 for the effect of statin on MB(VCAM) signal).; Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.
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:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:39
Deposited On:06 Dec 2013 09:36

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