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Uremic mouse model to study vascular calcification and “inflamm-aging”
Calcification and chronic inflammation of the vascular wall is a high-risk factor for cardiovascular mortality, especially in patients with chronic uremia. For the reduction or prevention of rapid disease progression, no specific treatment options are currently available. This study aimed to evaluat...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402761/ https://www.ncbi.nlm.nih.gov/pubmed/35916902 http://dx.doi.org/10.1007/s00109-022-02234-y |
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author | Tölle, Markus Henkel, Cornelia Herrmann, Jaqueline Daniel, Christoph Babic, Milen Xia, Mengdi Schulz, Anna M. Amann, Kerstin van der Giet, Markus Schuchardt, Mirjam |
author_facet | Tölle, Markus Henkel, Cornelia Herrmann, Jaqueline Daniel, Christoph Babic, Milen Xia, Mengdi Schulz, Anna M. Amann, Kerstin van der Giet, Markus Schuchardt, Mirjam |
author_sort | Tölle, Markus |
collection | PubMed |
description | Calcification and chronic inflammation of the vascular wall is a high-risk factor for cardiovascular mortality, especially in patients with chronic uremia. For the reduction or prevention of rapid disease progression, no specific treatment options are currently available. This study aimed to evaluate an adenine-based uremic mouse model for studying medial vessel calcification and senescence-associated secretory phenotype (SASP) changes of aortic tissue to unravel molecular pathogenesis and provide a model for therapy testing. The dietary adenine administration induced a stable and similar degree of chronic uremia in DBA2/N mice with an increase of uremia blood markers such as blood urea nitrogen, calcium, creatinine, alkaline phosphatase, and parathyroid hormone. Also, renal fibrosis and crystal deposits were detected upon adenine feeding. The uremic condition is related to a moderate to severe medial vessel calcification and subsequent elastin disorganization. In addition, expression of osteogenic markers as Bmp-2 and its transcription factor Sox-9 as well as p21 as senescence marker were increased in uremic mice compared to controls. Pro-inflammatory uremic proteins such as serum amyloid A, interleukin (Il)-1β, and Il-6 increased. This novel model of chronic uremia provides a simple method for investigation of signaling pathways in vascular inflammation and calcification and therefore offers an experimental basis for the development of potential therapeutic intervention studies. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00109-022-02234-y. |
format | Online Article Text |
id | pubmed-9402761 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-94027612022-08-26 Uremic mouse model to study vascular calcification and “inflamm-aging” Tölle, Markus Henkel, Cornelia Herrmann, Jaqueline Daniel, Christoph Babic, Milen Xia, Mengdi Schulz, Anna M. Amann, Kerstin van der Giet, Markus Schuchardt, Mirjam J Mol Med (Berl) Original Article Calcification and chronic inflammation of the vascular wall is a high-risk factor for cardiovascular mortality, especially in patients with chronic uremia. For the reduction or prevention of rapid disease progression, no specific treatment options are currently available. This study aimed to evaluate an adenine-based uremic mouse model for studying medial vessel calcification and senescence-associated secretory phenotype (SASP) changes of aortic tissue to unravel molecular pathogenesis and provide a model for therapy testing. The dietary adenine administration induced a stable and similar degree of chronic uremia in DBA2/N mice with an increase of uremia blood markers such as blood urea nitrogen, calcium, creatinine, alkaline phosphatase, and parathyroid hormone. Also, renal fibrosis and crystal deposits were detected upon adenine feeding. The uremic condition is related to a moderate to severe medial vessel calcification and subsequent elastin disorganization. In addition, expression of osteogenic markers as Bmp-2 and its transcription factor Sox-9 as well as p21 as senescence marker were increased in uremic mice compared to controls. Pro-inflammatory uremic proteins such as serum amyloid A, interleukin (Il)-1β, and Il-6 increased. This novel model of chronic uremia provides a simple method for investigation of signaling pathways in vascular inflammation and calcification and therefore offers an experimental basis for the development of potential therapeutic intervention studies. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00109-022-02234-y. Springer Berlin Heidelberg 2022-08-02 2022 /pmc/articles/PMC9402761/ /pubmed/35916902 http://dx.doi.org/10.1007/s00109-022-02234-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Tölle, Markus Henkel, Cornelia Herrmann, Jaqueline Daniel, Christoph Babic, Milen Xia, Mengdi Schulz, Anna M. Amann, Kerstin van der Giet, Markus Schuchardt, Mirjam Uremic mouse model to study vascular calcification and “inflamm-aging” |
title | Uremic mouse model to study vascular calcification and “inflamm-aging” |
title_full | Uremic mouse model to study vascular calcification and “inflamm-aging” |
title_fullStr | Uremic mouse model to study vascular calcification and “inflamm-aging” |
title_full_unstemmed | Uremic mouse model to study vascular calcification and “inflamm-aging” |
title_short | Uremic mouse model to study vascular calcification and “inflamm-aging” |
title_sort | uremic mouse model to study vascular calcification and “inflamm-aging” |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402761/ https://www.ncbi.nlm.nih.gov/pubmed/35916902 http://dx.doi.org/10.1007/s00109-022-02234-y |
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