Abstract 1541: Combination Therapy of Voluntary Exercise With Valsartan or Fluvastatin for Prevention of Atherosclerotic Lesion Development in Apolipoprotein E-Deficient Mice
Background: Sedentary lifestyle is associated with atherosclerotic disease. Previous studies have shown that exercise reduces cardiovascular disorders. However, it remains unclear whether voluntary exercise (VEx) and its combination therapy with antihypertensive or antihyperlipidemic agents affect the initiation and progression of atherosclerosis.
Methods: Study 1: Adult male apoE-deficient mice were fed a standard (STD) or high-cholesterol diet (HCD) for 10 weeks. Mice were divided into STD, HCD, and HCD+VEx groups. VEx was performed using wheel cage for 10 weeks. We assessed atherosclerotic lesions, endothelium-dependent relaxation of isolated aorta, lipids, and serum proinflammatory cytokines. Study 2: Combination therapy of VEx and administration of valsartan (0.5 mg/kg/day; HCD+VEx+V), or fluvastatin (3 mg/kg/day; HCD+VEx+F) using an osmotic minipump for 8 weeks were compared with the HCD+VEx, valsartan alone (HCD+V), and fluvastatin alone (HCD+F) groups.
Results: Study 1: No significant differences in lipid profiles were observed between the HCD and HCD+VEx groups. However, the areas of atherosclerotic lesions in the aortic sinus and thoracic aorta were significantly reduced in the HCD+VEx group than in the HCD group (P<0.001). A strong negative correlation between atherosclerotic areas and the mean running distance/day was observed (r=−0.90, P<0.01) in the HCD+VEx group. In the HCD+VEx group, an endothelial function was significantly preserved and significant reductions of IL-6 and TNF-α were demonstrated in comparison to the HCD group (all P<0.05). Study 2: Atherosclerotic lesion formation was significantly reduced in both the HCD+V and HCD+F groups in comparison with the HCD group. Notably, amplified reductions of atherosclerotic lesions were observed in the HCD+VEx+V and the HCD+VEx+F groups compared with the HCD+VEx, HCD+V, and HCD+F groups.
Conclusion: These results suggest that VEx ameliorates progression of endothelial dysfunction and atherosclerotic lesions via anti-inflammatory effects. In addition, the powerful impact of regular physical activity combined with anti-atherogenic medications must be recognized as an important strategy for reducing morbidity and mortality of atherosclerotic diseases.