title: Metoprolol reduces proinflammatory cytokines and atherosclerosis in ApoE-/- mice.
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 (P < 0.05 versus Control). Further, metoprolol reduced serum TNFα and the chemokine CXCL1 (P < 0.01 versus Control for both) as well as decreasing the macrophage content in the plaques (P < 0.01 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.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Ulleryd
authors.affiliation: The 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.
authors.forename: Evelina
authors.initials: E
authors.lastname: Bernberg
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
authors.forename: Li Jin
authors.initials: LJ
authors.lastname: Yang
authors.affiliation: The 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.
authors.forename: Göran M L
authors.initials: GM
authors.lastname: Bergström
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Johansson
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D054360:Chemokine CXCL1 / Q000097:blood*; D002784:Cholesterol / Q000097:blood / Q000235:genetics; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001057:Apolipoproteins E; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D008790:Metoprolol
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