Areas Of Thoracic Aorta Research Articles

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

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.

Dietary salt restriction accelerates atherosclerosis in apolipoprotein E-deficient mice

Background: Whether a general reduction in salt intake reduces or actually enhances cardiovascular mortality in man remains an issue of controversy. Low sodium diets may lead to adverse side effects by stimulating the renin–angiotensin and sympathetic nervous systems. The present study was designed to investigate the effects of low dietary salt on atherosclerotic lesion progression in apolipoprotein E deficient (apoE −/−) mice. Methods and results: We fed 7-week-old apoE −/− mice on low (0.036% NaCl; n = 28) or regular (0.64% NaCl; n = 26) salt diets for 16 weeks. At the age of 23 weeks, the cross-section surface area of atherosclerotic plaques was measured in aortic root and thoracic aorta. Serum total cholesterol, triglycerides, plasma angiotensin levels and urinary protein/creatinine concentrations were assessed. Exposure to low salt caused significant increases in atherosclerotic lesion surface area in thoracic aorta, but did not alter lesion area in aortic root. Low-salt mice also had higher serum total cholesterol and higher plasma angiotensin II (ANG-II) concentrations. Atherosclerotic lesion area was correlated with ANG-II levels in low-salt but not in regular-salt animals, and with total cholesterol concentration in all mice. Mean arterial pressure was comparable in both groups. Conclusions: Dietary salt restriction accelerated atherosclerotic lesion formation in apoE −/− mice through a mechanism that is probably related to ANG-II formation. Whether these findings are relevant to human cardiovascular disease remains to be evaluated.

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