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01-12-2022 | Cardiomyopathy | Research

Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages

Authors: M. A. Mawhin, R. G. Bright, J. D. Fourre, E. I. Vloumidi, J. Tomlinson, A. Sardini, C. D. Pusey, K. J. Woollard

Published in: BMC Nephrology | Issue 1/2022

Abstract

Background

The leading cause of death in end-stage kidney disease is related to cardiovascular disease. Macrophages are known to be involved in both chronic kidney disease (CKD) and heart failure, however their role in the development of cardiorenal syndrome is less clear. We thus sought to investigate the role of macrophages in uremic cardiac disease.

Methods

We assessed cardiac response in two experimental models of CKD and tested macrophage and chemokine implication in monocytopenic CCR2^−/− and anti-CXCL10 treated mice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSC-derived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors.

Results

We found that reduced kidney function resulted in the expansion of cardiac macrophages, in particular through local proliferation of resident populations. Influx of circulating monocytes contributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophage expansion in uremic disease. In humans, we found increased plasma CXCL10 concentrations in advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiac fibroblasts.

Conclusions

This study provides new insight into the role of the innate immune system in uremic cardiomyopathy.

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Title: Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages
Authors: M. A. Mawhin
R. G. Bright
J. D. Fourre
E. I. Vloumidi
J. Tomlinson
A. Sardini
C. D. Pusey
K. J. Woollard
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Cardiomyopathy
Chronic Kidney Disease
Published in: BMC Nephrology / Issue 1/2022
Electronic ISSN: 1471-2369
DOI: https://doi.org/10.1186/s12882-021-02593-7

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Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages

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