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BioMed Research International
Volume 2014 (2014), Article ID 548783, 7 pages
http://dx.doi.org/10.1155/2014/548783
Research Article

Metoprolol Reduces Proinflammatory Cytokines and Atherosclerosis in ApoE−/− Mice

1Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden
2The Wallenberg Laboratory, Department of Molecular and Clinical Medicine/Clinical Physiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden

Received 11 April 2014; Accepted 20 June 2014; Published 8 July 2014

Academic Editor: Ban-Hock Toh

Copyright © 2014 Marcus A. Ulleryd et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist) may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE−/− mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE−/− mice were treated with metoprolol (2.5 mg/kg/h) or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta ( versus Control). Further, metoprolol reduced serum TNFα and the chemokine CXCL1 ( versus Control for both) as well as decreasing the macrophage content in the plaques ( versus Control). Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE−/− mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFα and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect.