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Metoprolol reduces proinflammatory cytokines and atherosclerosis in ApoE-/- mice.

Ulleryd MA, Bernberg E, Yang LJ, Bergström GM, Johansson ME - Biomed Res Int (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.

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.

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Metoprolol decreases atherosclerosis. (a)-(b) Metoprolol treatment (2.5 mg/kg per hour) decreased atherosclerotic plaque area in thoracic aorta. (c)-(d) A similar trend was seen in the aortic root, although this did not reach significance (P = 0.053). (e)-(f) Metoprolol treatment decreased the macrophage content in aortic lesions. Representative micrographs of thoracic aorta stained with Sudan IV (b), aortic root stained with Oil Red O (d), and macrophage marker Mac-2 (f). Left panel: Controls; right panel: metoprolol treated. Scale bar represents 200 μm. *P < 0.05, **P < 0.01 versus Control.
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fig2: Metoprolol decreases atherosclerosis. (a)-(b) Metoprolol treatment (2.5 mg/kg per hour) decreased atherosclerotic plaque area in thoracic aorta. (c)-(d) A similar trend was seen in the aortic root, although this did not reach significance (P = 0.053). (e)-(f) Metoprolol treatment decreased the macrophage content in aortic lesions. Representative micrographs of thoracic aorta stained with Sudan IV (b), aortic root stained with Oil Red O (d), and macrophage marker Mac-2 (f). Left panel: Controls; right panel: metoprolol treated. Scale bar represents 200 μm. *P < 0.05, **P < 0.01 versus Control.

Mentions: Eleven weeks of metoprolol treatment significantly decreased atherosclerotic plaque area in thoracic aorta (P < 0.05, Figures 2(a) and 2(b)). A similar pattern was seen in the aortic root; however, this did not reach significance (P = 0.053, Figures 2(c) and 2(d)).


Metoprolol reduces proinflammatory cytokines and atherosclerosis in ApoE-/- mice.

Ulleryd MA, Bernberg E, Yang LJ, Bergström GM, Johansson ME - Biomed Res Int (2014)

Metoprolol decreases atherosclerosis. (a)-(b) Metoprolol treatment (2.5 mg/kg per hour) decreased atherosclerotic plaque area in thoracic aorta. (c)-(d) A similar trend was seen in the aortic root, although this did not reach significance (P = 0.053). (e)-(f) Metoprolol treatment decreased the macrophage content in aortic lesions. Representative micrographs of thoracic aorta stained with Sudan IV (b), aortic root stained with Oil Red O (d), and macrophage marker Mac-2 (f). Left panel: Controls; right panel: metoprolol treated. Scale bar represents 200 μm. *P < 0.05, **P < 0.01 versus Control.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4109227&req=5

fig2: Metoprolol decreases atherosclerosis. (a)-(b) Metoprolol treatment (2.5 mg/kg per hour) decreased atherosclerotic plaque area in thoracic aorta. (c)-(d) A similar trend was seen in the aortic root, although this did not reach significance (P = 0.053). (e)-(f) Metoprolol treatment decreased the macrophage content in aortic lesions. Representative micrographs of thoracic aorta stained with Sudan IV (b), aortic root stained with Oil Red O (d), and macrophage marker Mac-2 (f). Left panel: Controls; right panel: metoprolol treated. Scale bar represents 200 μm. *P < 0.05, **P < 0.01 versus Control.
Mentions: Eleven weeks of metoprolol treatment significantly decreased atherosclerotic plaque area in thoracic aorta (P < 0.05, Figures 2(a) and 2(b)). A similar pattern was seen in the aortic root; however, this did not reach significance (P = 0.053, Figures 2(c) and 2(d)).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, P.O. Box 432, 405 30 Gothenburg, Sweden.

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.

Show MeSH
Related in: MedlinePlus