Abstract
Cardiovascular disease is the main cause of morbidity and mortality in patients with kidney disease. The effectiveness of exercise for cardiovascular disease that is accelerated by the presence of chronic kidney disease remains unknown. The present study utilized apolipoprotein E knockout mice with 5/6 nephrectomy as a model of combined kidney disease and cardiovascular disease to investigate the effect of exercise on aortic plaque formation, vascular function and systemic inflammation. Animals were randomly assigned to nephrectomy or control and then to either voluntary wheel running exercise or sedentary. Following 12-weeks, aortic plaque area was significantly (p<0.05, d=1.2) lower in exercising nephrectomised mice compared to sedentary nephrectomised mice. There was a strong, negative correlation between average distance run each week and plaque area in nephrectomised and control mice (r=–0.76, p=0.048 and r=–0.73, p=0.062; respectively). In vitro aortic contraction and endothelial-independent and endothelial-dependent relaxation were not influenced by exercise (p>0.05). Nephrectomy increased IL-6 and TNF-α concentrations compared with control mice (p<0.001 and p<0.05, respectively), while levels of IL-10, MCP-1 and MIP-1α were not significantly influenced by nephrectomy or voluntary exercise (p>0.05). Exercise was an effective non-pharmacologic approach to slow cardiovascular disease in the presence of kidney disease in the apolipoprotein E knockout mouse.
Highlights
The progression of chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality [1], that is greater than traditional risk factors such dyslipidemia, hypertension and diabetes alone can account for
The present study suggests that voluntary exercise is effective in limiting aortic plaque area in the apoE-/- mouse model of CKD using 5/6 nephrectomy
The onset of CKD in apoE-/- mice accelerates atherosclerosis [9,10,11] and increases thickening of the aortic valves [12], in combination with elevating inflammatory cytokines. These mice display reduced glomerular filtration rate and increased plasma creatinine levels compared with wild type controls [8], supporting that CKD is associated with the progression of atherosclerosis
Summary
The progression of chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality [1], that is greater than traditional risk factors such dyslipidemia, hypertension and diabetes alone can account for. Strategies targeted at reducing non-traditional risk factors such as oxidative stress, inflammation and endothelial dysfunction may prove effective treatment in the early stages of CKD, with the potential to slow the decline in kidney function and associated cardiovascular disease [3]. Exercise has proven beneficial in reducing cardiovascular disease risk factors [4]. Whereas the benefits of exercise for cardiovascular disease risk are well recognised, the effect of exercise on plaque formation in a model of cardiovascular disease and CKD is yet to be determined
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