ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model.
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).


CONCLUSIONS
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.
Simolin
Mikko A
MA
Wihuri Research Institute, Helsinki, Finland. mikko.simolin@helsinki.fi
Pedersen
Tanja X
TX
Bro
Susanne
S
Mäyränpää
Mikko I
MI
Helske
Satu
S
Nielsen
Lars B
LB
Kovanen
Petri T
PT
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001021:Aortic Valve / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004656:Enalapril / Q000008:administration & dosage*; D005355:Fibrosis / Q000188:drug therapy*; D006949:Hyperlipidemias; D007668:Kidney / Q000473:pathology / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D014508:Urea / Q000097:blood; D014511:Uremia
D000806:Angiotensin-Converting Enzyme Inhibitors; D001057:Apolipoproteins E; D004656:Enalapril; D014508:Urea; D003404:Creatinine