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Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure

Introduction. This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed,...

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Autores principales: Messaoudi, Hind, Levesque, Thomas, Perzo, Nicolas, Berg, Elodie, Feugray, Guillaume, Dumesnil, Anaïs, Brunel, Valéry, Guerrot, Dominique, Eltchaninoff, Hélène, Richard, Vincent, Kamel, Saïd, Durand, Eric, Bennis, Youssef, Bellien, Jérémy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963294/
https://www.ncbi.nlm.nih.gov/pubmed/36836075
http://dx.doi.org/10.3390/jcm12041539
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author Messaoudi, Hind
Levesque, Thomas
Perzo, Nicolas
Berg, Elodie
Feugray, Guillaume
Dumesnil, Anaïs
Brunel, Valéry
Guerrot, Dominique
Eltchaninoff, Hélène
Richard, Vincent
Kamel, Saïd
Durand, Eric
Bennis, Youssef
Bellien, Jérémy
author_facet Messaoudi, Hind
Levesque, Thomas
Perzo, Nicolas
Berg, Elodie
Feugray, Guillaume
Dumesnil, Anaïs
Brunel, Valéry
Guerrot, Dominique
Eltchaninoff, Hélène
Richard, Vincent
Kamel, Saïd
Durand, Eric
Bennis, Youssef
Bellien, Jérémy
author_sort Messaoudi, Hind
collection PubMed
description Introduction. This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed, the latter contributes to the high morbidity and mortality of CKD patients and sorely lacks preclinical models for pathophysiological and pharmacological studies. Methods. Renal and cardiovascular function and structure were compared between sham-operated and 5/6 Nx rats + P 10 to 12 weeks after surgery. Results. As expected, 11 weeks after surgery, 5/6Nx + P rats developed CKD as demonstrated by their increase in plasma creatinine and urea nitrogen and decrease in glomerular filtration rate, estimated by using fluorescein-isothiocyanate-labelled sinistrin, anemia, polyuria, and polydipsia compared to sham-operated animals on a normal-phosphorus diet. At the vascular level, 5/6Nx + P rats had an increase in the calcium content of the aorta; a decrease in mesenteric artery dilatation in response to a stepwise increase in flow, illustrating the vascular dysfunction; and an increase in blood pressure. Moreover, immunohistology showed a marked deposition of hydroxyapatite crystals in the aortic valve of 5/6Nx + P rats. Echocardiography demonstrated that this was associated with a decrease in aortic valve cusp separation and an increase in aortic valve mean pressure gradient and in peak aortic valve velocity. Left-ventricular diastolic and systolic dysfunction as well as fibrosis were also present in 5/6Nx + P rats. Conclusion. This study demonstrates that 5/6Nx + P recapitulates the cardiovascular consequences observed in humans with CKD. In particular, the initiation of CAVD was shown, highlighting the interest of this animal model to study the mechanisms involved in the development of aortic stenosis and test new therapeutic strategies at an early stage of the disease.
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spelling pubmed-99632942023-02-26 Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure Messaoudi, Hind Levesque, Thomas Perzo, Nicolas Berg, Elodie Feugray, Guillaume Dumesnil, Anaïs Brunel, Valéry Guerrot, Dominique Eltchaninoff, Hélène Richard, Vincent Kamel, Saïd Durand, Eric Bennis, Youssef Bellien, Jérémy J Clin Med Article Introduction. This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed, the latter contributes to the high morbidity and mortality of CKD patients and sorely lacks preclinical models for pathophysiological and pharmacological studies. Methods. Renal and cardiovascular function and structure were compared between sham-operated and 5/6 Nx rats + P 10 to 12 weeks after surgery. Results. As expected, 11 weeks after surgery, 5/6Nx + P rats developed CKD as demonstrated by their increase in plasma creatinine and urea nitrogen and decrease in glomerular filtration rate, estimated by using fluorescein-isothiocyanate-labelled sinistrin, anemia, polyuria, and polydipsia compared to sham-operated animals on a normal-phosphorus diet. At the vascular level, 5/6Nx + P rats had an increase in the calcium content of the aorta; a decrease in mesenteric artery dilatation in response to a stepwise increase in flow, illustrating the vascular dysfunction; and an increase in blood pressure. Moreover, immunohistology showed a marked deposition of hydroxyapatite crystals in the aortic valve of 5/6Nx + P rats. Echocardiography demonstrated that this was associated with a decrease in aortic valve cusp separation and an increase in aortic valve mean pressure gradient and in peak aortic valve velocity. Left-ventricular diastolic and systolic dysfunction as well as fibrosis were also present in 5/6Nx + P rats. Conclusion. This study demonstrates that 5/6Nx + P recapitulates the cardiovascular consequences observed in humans with CKD. In particular, the initiation of CAVD was shown, highlighting the interest of this animal model to study the mechanisms involved in the development of aortic stenosis and test new therapeutic strategies at an early stage of the disease. MDPI 2023-02-15 /pmc/articles/PMC9963294/ /pubmed/36836075 http://dx.doi.org/10.3390/jcm12041539 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Messaoudi, Hind
Levesque, Thomas
Perzo, Nicolas
Berg, Elodie
Feugray, Guillaume
Dumesnil, Anaïs
Brunel, Valéry
Guerrot, Dominique
Eltchaninoff, Hélène
Richard, Vincent
Kamel, Saïd
Durand, Eric
Bennis, Youssef
Bellien, Jérémy
Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure
title Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure
title_full Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure
title_fullStr Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure
title_full_unstemmed Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure
title_short Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure
title_sort subtotal nephrectomy associated with a high-phosphate diet in rats mimics the development of calcified aortic valve disease associated with chronic renal failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963294/
https://www.ncbi.nlm.nih.gov/pubmed/36836075
http://dx.doi.org/10.3390/jcm12041539
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