Atherosclerosis and Vascular Calcification in Uremia: Lessons from a New Mouse Model of Ckd

Accelerated calcifying atherosclerosis, medial calcification, and valvular calcification are hallmarks of cardiovascular disease in the uremic population. We surgically induced chronic kidney disease in apolipoprotein E deficient (apoE-/-)mice to study a possible acceleration of aortic atherosclerosis, the degree and type of vascular calcification as well as factors involved in the calcification process. Atherosclerotic lesions and vascular calcification were significantly larger in uremic apoE-/- mice than in non-uraemic controls. The accelerated atherosclerosis was associated with an increase in aortic nitrotyrosine expression, indicating enhanced oxidative stress, and an increase in plaque collagen content, indicating changes in plaque composition. N-acetylcysteine treatment slowed the rapid progression of atherosclerotic lesions and reversed the increase in plaque collagen content compared with placebo treatment. Sevelamer treatment delayed not only vascular calcification but also atherosclerotic lesion progression in uraemic apoE-/- mice. These treatment effects also were associated with diminished oxidative stress and were independent of cholesterol lowering