Cargando…

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. METHO...

Descripción completa

Detalles Bibliográficos
Autores principales: Simolin, Mikko A, Pedersen, Tanja X, Bro, Susanne, Mäyränpää, Mikko I, Helske, Satu, Nielsen, Lars B, Kovanen, Petri T
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663538/
https://www.ncbi.nlm.nih.gov/pubmed/19257900
http://dx.doi.org/10.1186/1471-2261-9-10
_version_ 1782165902897184768
author Simolin, Mikko A
Pedersen, Tanja X
Bro, Susanne
Mäyränpää, Mikko I
Helske, Satu
Nielsen, Lars B
Kovanen, Petri T
author_facet Simolin, Mikko A
Pedersen, Tanja X
Bro, Susanne
Mäyränpää, Mikko I
Helske, Satu
Nielsen, Lars B
Kovanen, Petri T
author_sort Simolin, Mikko A
collection PubMed
description 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.
format Text
id pubmed-2663538
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-26635382009-04-01 ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model Simolin, Mikko A Pedersen, Tanja X Bro, Susanne Mäyränpää, Mikko I Helske, Satu Nielsen, Lars B Kovanen, Petri T BMC Cardiovasc Disord Research Article 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. BioMed Central 2009-03-03 /pmc/articles/PMC2663538/ /pubmed/19257900 http://dx.doi.org/10.1186/1471-2261-9-10 Text en Copyright © 2009 Simolin et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Simolin, Mikko A
Pedersen, Tanja X
Bro, Susanne
Mäyränpää, Mikko I
Helske, Satu
Nielsen, Lars B
Kovanen, Petri T
ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
title ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
title_full ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
title_fullStr ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
title_full_unstemmed ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
title_short ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
title_sort ace inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663538/
https://www.ncbi.nlm.nih.gov/pubmed/19257900
http://dx.doi.org/10.1186/1471-2261-9-10
work_keys_str_mv AT simolinmikkoa aceinhibitionattenuatesuremiainducedaorticvalvethickeninginanovelmousemodel
AT pedersentanjax aceinhibitionattenuatesuremiainducedaorticvalvethickeninginanovelmousemodel
AT brosusanne aceinhibitionattenuatesuremiainducedaorticvalvethickeninginanovelmousemodel
AT mayranpaamikkoi aceinhibitionattenuatesuremiainducedaorticvalvethickeninginanovelmousemodel
AT helskesatu aceinhibitionattenuatesuremiainducedaorticvalvethickeninginanovelmousemodel
AT nielsenlarsb aceinhibitionattenuatesuremiainducedaorticvalvethickeninginanovelmousemodel
AT kovanenpetrit aceinhibitionattenuatesuremiainducedaorticvalvethickeninginanovelmousemodel