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Background We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE -/- ) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril. Methods Thickening of the aortic valve leaflets in apoE -/- mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots. Results Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014). Conclusion Moderate uremia causes thickening of the aortic valves in apoE -/- mice, which can be attenuated by ACE inhibition. The nephrectomized apoE -/- mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.