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.
Highlights
Cardiovascular events are most often caused by complications to atherosclerotic disease. β-Blockers have been shown to reduce the risk of cardiovascular events after myocardial infarction [1, 2]
It has been shown in two separate studies that low-dose metoprolol administered during three years slows the progression of intima media thickness (IMT) in humans [10, 11] and alters the grey scale of carotid plaques [12]
In the present study we demonstrated that treatment with a moderate dose of the selective β1-adrenoceptor antagonist metoprolol reduced atherosclerotic plaque area in ApoE−/− mice
Summary
Cardiovascular events are most often caused by complications to atherosclerotic disease. β-Blockers have been shown to reduce the risk of cardiovascular events after myocardial infarction [1, 2]. Β-Blockers have been shown to reduce the risk of cardiovascular events after myocardial infarction [1, 2]. The protective effect of metoprolol was seen under nonstressed conditions in rabbit models of atherosclerosis [9] It has been shown in two separate studies that low-dose metoprolol administered during three years slows the progression of intima media thickness (IMT) in humans [10, 11] and alters the grey scale of carotid plaques [12]. Despite these convincing data, the mechanisms behind this protective effect have not yet been established
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