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Cardiac remodeling associated with chronic kidney disease is enhanced in a rat model of metabolic syndrome: Preparation of mesenchymal transition

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Abstract

Cardiac alteration due to chronic kidney disease is described by tissue fibrosis. This remodeling involves myofibroblasts of various origins, including epithelial or endothelial to mesenchymal transitions. In addition, obesity and insulin resistance together or separately seem to exacerbate cardiovascular risk in chronic kidney disease (CKD). The main objective of this study was to assess if pre-existing metabolic disease exacerbates CKD-induced cardiac alterations. In addition, we hypothesised that endothelial to mesenchymal transition participates in this enhancement of cardiac fibrosis. Rats fed cafeteria type diet for 6 months underwent a subtotal nephrectomy at 4 months. Cardiac fibrosis was evaluated by histology and qRT-PCR. Collagens and macrophages were quantified by immunohistochemistry. Endothelial to mesenchymal transitions were assessed by qRT-PCR (CD31, VE-cadherin, α-SMA, nestin) and also by CD31 immunofluorescence staining. Rats fed with cafeteria type regimen were obese, hypertensive and insulin resistant. Cardiac fibrosis was predominant in CKD rats and was highly majored by cafeteria regimen. Collagen-1 and nestin expressions were higher in CKD rats, independently of regimen. Interestingly, in rats with CKD and cafeteria diet we found an increase of CD31 and α-SMA co-staining with suggest an implication of endothelial to mesenchymal transition during heart fibrosis. We showed that rats already obese and insulin resistant had an enhanced cardiac alteration to a subsequent renal injury. Cardiac fibrosis process could be supported by a involvement of the endothelial to mesenchymal transition phenomenon.

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Data Availability

All data will be available upon reasonable request by sending an email to: fabrice.raynaud1@umontpellier.fr

Abbreviations

CKD:

Chronic kidney disease

EndMT:

Endothelial to mesenchymal transition

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Authors and Affiliations

  1. PHYMEDEXP, Université de Montpellier, INSERM, CNRS, Montpellier, France

    Maëlle Plawecki, Anthony Chauvin, Jean-Paul Cristol, Bernard Jover & Fabrice Raynaud

  2. RD Néphrologie, Montpellier, France

    Nathalie Gayrard

  3. BC2M, Université de Montpellier, Montpellier, France

    Laura Jeanson & Anne-Dominique Lajoix

  4. Laboratoire de Biochimie et d’hormonologie, CHU Lapeyronie, Montpellier, France

    Maëlle Plawecki & Jean-Paul Cristol

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  1. Maëlle Plawecki
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  2. Nathalie Gayrard
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  3. Laura Jeanson
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JB, RF, wrote the main manuscript text MP, NG, AC, LJ, RF performed experiments All authors reviewed the manuscript.

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Correspondence to Fabrice Raynaud.

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Plawecki, M., Gayrard, N., Jeanson, L. et al. Cardiac remodeling associated with chronic kidney disease is enhanced in a rat model of metabolic syndrome: Preparation of mesenchymal transition. Mol Cell Biochem 479, 29–39 (2024). https://doi.org/10.1007/s11010-023-04710-6

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