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A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System

Chronic kidney disease (CKD) is a significant public health challenge with a substantial associated risk of mortality, morbidity, and health care expenditure. Culprits that lead to development and progression of CKD are multifaceted and heterogenous in nature. This notion underscores the need for di...

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Autores principales: Machado, Sarah E, Spangler, Daryll, Black, Laurence M., Traylor, Amie M., Balla, József, Zarjou, Abolfazl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099146/
https://www.ncbi.nlm.nih.gov/pubmed/35574469
http://dx.doi.org/10.3389/fphys.2022.897179
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author Machado, Sarah E
Spangler, Daryll
Black, Laurence M.
Traylor, Amie M.
Balla, József
Zarjou, Abolfazl
author_facet Machado, Sarah E
Spangler, Daryll
Black, Laurence M.
Traylor, Amie M.
Balla, József
Zarjou, Abolfazl
author_sort Machado, Sarah E
collection PubMed
description Chronic kidney disease (CKD) is a significant public health challenge with a substantial associated risk of mortality, morbidity, and health care expenditure. Culprits that lead to development and progression of CKD are multifaceted and heterogenous in nature. This notion underscores the need for diversification of animal models to investigate its pathophysiology, related complications, and to subsequently enable discovery of novel therapeutics. Importantly, animal models that could recapitulate complications of CKD in both genders are desperately needed. Cardiovascular disease is the most common cause of death in CKD patients that may be due in part to high prevalence of vascular calcification (VC). Using DBA/2 mice that are susceptible to development of VC, we sought to investigate the feasibility and reproducibility of a unilateral ischemia-reperfusion model followed by contralateral nephrectomy (UIRI/Nx) to induce CKD and its related complications in female and male mice. Our results demonstrate that irrespective of gender, mice faithfully displayed complications of moderate CKD following UIRI/Nx as evidenced by significant rise in serum creatinine, albuminuria, higher degree of collagen deposition, elevated expression of classic fibrotic markers, higher circulating levels of FGF-23, PTH and hepcidin. Moreover, we corroborate the osteoblastic transition of aortic smooth muscle cells and cardiomyocytes based on higher levels of osteoblastic markers namely, Cbfa-1, osteopontin, osteocalcin, and osterix. Our data confirms a viable, and consistent model of moderate CKD and its associated complications in both male and female mice. Furthermore, early evidence of osteoblastic transition of cardiovascular system in this model confirms its suitability for studying and implementing potential preventive and/or therapeutic approaches that are urgently needed in this field.
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spelling pubmed-90991462022-05-14 A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System Machado, Sarah E Spangler, Daryll Black, Laurence M. Traylor, Amie M. Balla, József Zarjou, Abolfazl Front Physiol Physiology Chronic kidney disease (CKD) is a significant public health challenge with a substantial associated risk of mortality, morbidity, and health care expenditure. Culprits that lead to development and progression of CKD are multifaceted and heterogenous in nature. This notion underscores the need for diversification of animal models to investigate its pathophysiology, related complications, and to subsequently enable discovery of novel therapeutics. Importantly, animal models that could recapitulate complications of CKD in both genders are desperately needed. Cardiovascular disease is the most common cause of death in CKD patients that may be due in part to high prevalence of vascular calcification (VC). Using DBA/2 mice that are susceptible to development of VC, we sought to investigate the feasibility and reproducibility of a unilateral ischemia-reperfusion model followed by contralateral nephrectomy (UIRI/Nx) to induce CKD and its related complications in female and male mice. Our results demonstrate that irrespective of gender, mice faithfully displayed complications of moderate CKD following UIRI/Nx as evidenced by significant rise in serum creatinine, albuminuria, higher degree of collagen deposition, elevated expression of classic fibrotic markers, higher circulating levels of FGF-23, PTH and hepcidin. Moreover, we corroborate the osteoblastic transition of aortic smooth muscle cells and cardiomyocytes based on higher levels of osteoblastic markers namely, Cbfa-1, osteopontin, osteocalcin, and osterix. Our data confirms a viable, and consistent model of moderate CKD and its associated complications in both male and female mice. Furthermore, early evidence of osteoblastic transition of cardiovascular system in this model confirms its suitability for studying and implementing potential preventive and/or therapeutic approaches that are urgently needed in this field. Frontiers Media S.A. 2022-04-29 /pmc/articles/PMC9099146/ /pubmed/35574469 http://dx.doi.org/10.3389/fphys.2022.897179 Text en Copyright © 2022 Machado, Spangler, Black, Traylor, Balla and Zarjou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Machado, Sarah E
Spangler, Daryll
Black, Laurence M.
Traylor, Amie M.
Balla, József
Zarjou, Abolfazl
A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System
title A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System
title_full A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System
title_fullStr A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System
title_full_unstemmed A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System
title_short A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System
title_sort reproducible mouse model of moderate ckd with early manifestations of osteoblastic transition of cardiovascular system
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099146/
https://www.ncbi.nlm.nih.gov/pubmed/35574469
http://dx.doi.org/10.3389/fphys.2022.897179
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