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

Simolin MA, Pedersen TX, Bro S, Mäyränpää MI, Helske S, Nielsen LB, Kovanen PT - BMC Cardiovasc Disord (2009)

Bottom Line: 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.The maximal thickness of each leaflet was measured from histological sections of the aortic roots.Moderate uremia causes thickening of the aortic valves in apoE-/- mice, which can be attenuated by ACE inhibition.

View Article: PubMed Central - HTML - PubMed

Affiliation: Wihuri Research Institute, Helsinki, Finland. mikko.simolin@helsinki.fi

ABSTRACT

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.

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Flowcharts showing the study designs in Study 1 and Study 2.
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Figure 1: Flowcharts showing the study designs in Study 1 and Study 2.

Mentions: We examined the valvular leaflets in hearts from mice that were also used to study the effects of uremia on the development of atherosclerosis [21,22]. The studies were performed according to the principles stated in the Danish law on animal experiments and approved by the Animal Experiments Inspectorate, Ministry of Justice, Denmark. The animals were male apoE-/- mice (C57BL/6JBom-ApoEtm1Unc), which had been backcrossed 10 generations onto the C57BL/6 background (M&B Laboratory Animals and Services for Biomedical Research, Ry, Denmark) and fed with a standard mouse diet (Altromin 1314, Altromin, Lage, Germany). The investigation was divided into two substudies, which are referred to as Study 1 and Study 2 in the text. The study design of both studies is shown in Figure 1.


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

Simolin MA, Pedersen TX, Bro S, Mäyränpää MI, Helske S, Nielsen LB, Kovanen PT - BMC Cardiovasc Disord (2009)

Flowcharts showing the study designs in Study 1 and Study 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2663538&req=5

Figure 1: Flowcharts showing the study designs in Study 1 and Study 2.
Mentions: We examined the valvular leaflets in hearts from mice that were also used to study the effects of uremia on the development of atherosclerosis [21,22]. The studies were performed according to the principles stated in the Danish law on animal experiments and approved by the Animal Experiments Inspectorate, Ministry of Justice, Denmark. The animals were male apoE-/- mice (C57BL/6JBom-ApoEtm1Unc), which had been backcrossed 10 generations onto the C57BL/6 background (M&B Laboratory Animals and Services for Biomedical Research, Ry, Denmark) and fed with a standard mouse diet (Altromin 1314, Altromin, Lage, Germany). The investigation was divided into two substudies, which are referred to as Study 1 and Study 2 in the text. The study design of both studies is shown in Figure 1.

Bottom Line: 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.The maximal thickness of each leaflet was measured from histological sections of the aortic roots.Moderate uremia causes thickening of the aortic valves in apoE-/- mice, which can be attenuated by ACE inhibition.

View Article: PubMed Central - HTML - PubMed

Affiliation: Wihuri Research Institute, Helsinki, Finland. mikko.simolin@helsinki.fi

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus