Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure
<b>Introduction.</b> 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 disea...
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MDPI AG
2023-02-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/4/1539 |
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| author | Hind Messaoudi Thomas Levesque Nicolas Perzo Elodie Berg Guillaume Feugray Anaïs Dumesnil Valéry Brunel Dominique Guerrot Hélène Eltchaninoff Vincent Richard Saïd Kamel Eric Durand Youssef Bennis Jérémy Bellien |
| author_facet | Hind Messaoudi Thomas Levesque Nicolas Perzo Elodie Berg Guillaume Feugray Anaïs Dumesnil Valéry Brunel Dominique Guerrot Hélène Eltchaninoff Vincent Richard Saïd Kamel Eric Durand Youssef Bennis Jérémy Bellien |
| author_sort | Hind Messaoudi |
| collection | DOAJ |
| description | <b>Introduction.</b> 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. <b>Methods.</b> Renal and cardiovascular function and structure were compared between sham-operated and 5/6 Nx rats + P 10 to 12 weeks after surgery. <b>Results.</b> 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. <b>Conclusion.</b> 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. |
| first_indexed | 2024-03-11T08:37:19Z |
| format | Article |
| id | doaj.art-0bfedff6a9384ed6bc4c6e403050743e |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-11T08:37:19Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-0bfedff6a9384ed6bc4c6e403050743e2023-11-16T21:21:01ZengMDPI AGJournal of Clinical Medicine2077-03832023-02-01124153910.3390/jcm12041539Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal FailureHind Messaoudi0Thomas Levesque1Nicolas Perzo2Elodie Berg3Guillaume Feugray4Anaïs Dumesnil5Valéry Brunel6Dominique Guerrot7Hélène Eltchaninoff8Vincent Richard9Saïd Kamel10Eric Durand11Youssef Bennis12Jérémy Bellien13INSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceDepartment of General Biochemistry, CHU Rouen, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceUR UPJV 7517, Mécanismes Physiopathologiques et Conséquences des Calcifications Cardiovasculaires (MP3CV), Centre de Recherche Universitaire en Santé, Université de Picardie Jules Verne, F-80054 Amiens, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, FranceINSERM EnVI UMR 1096, University of Rouen Normandie, F-76000 Rouen, France<b>Introduction.</b> 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. <b>Methods.</b> Renal and cardiovascular function and structure were compared between sham-operated and 5/6 Nx rats + P 10 to 12 weeks after surgery. <b>Results.</b> 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. <b>Conclusion.</b> 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.https://www.mdpi.com/2077-0383/12/4/1539animal modelchronic kidney diseasecardiovascular complicationscalcified aortic valve disease |
| spellingShingle | Hind Messaoudi Thomas Levesque Nicolas Perzo Elodie Berg Guillaume Feugray Anaïs Dumesnil Valéry Brunel Dominique Guerrot Hélène Eltchaninoff Vincent Richard Saïd Kamel Eric Durand Youssef Bennis Jérémy Bellien Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure Journal of Clinical Medicine animal model chronic kidney disease cardiovascular complications calcified aortic valve disease |
| 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 | animal model chronic kidney disease cardiovascular complications calcified aortic valve disease |
| url | https://www.mdpi.com/2077-0383/12/4/1539 |
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