ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | BMC Cardiovascular Disorders |
Volume | 9 |
Pages (from-to) | 10 |
Number of pages | 1 |
ISSN | 1471-2261 |
DOIs | |
Publication status | Published - 2009 |
Bibliographical note
Keywords: Angiotensin-Converting Enzyme Inhibitors; Animals; Aortic Valve; Aortic Valve Stenosis; Apolipoproteins E; Creatinine; Disease Models, Animal; Enalapril; Fibrosis; Hyperlipidemias; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nephrectomy; Renal Insufficiency; Renin-Angiotensin System; Urea; Uremia
ID: 17343320