Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages
File(s)
Published version
Author(s)
Type
Journal Article
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 iPSCderived 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.
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 iPSCderived 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.
Date Issued
2022-01-28
Date Acceptance
2021-11-01
Citation
BMC Nephrology, 2022, 23 (47), pp.1-15
ISSN
1471-2369
Publisher
BioMed Central
Start Page
1
End Page
15
Journal / Book Title
BMC Nephrology
Volume
23
Issue
47
Copyright Statement
© The Author(s) 2022. Open Access This 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/. The Creative Commons Public Domain Dedication waiver (http://creativeco
mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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/. The Creative Commons Public Domain Dedication waiver (http://creativeco
mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
License URL
Identifier
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-021-02593-7
Subjects
Science & Technology
Life Sciences & Biomedicine
Urology & Nephrology
uremic cardiomyopathy
macrophages
chemokine
CKD
HEART-FAILURE
STEADY-STATE
RECRUITMENT
MECHANISMS
MONOCYTES
CXCL10
CELLS
GLOMERULOSCLEROSIS
EPIDEMIOLOGY
NEPHROPATHY
CKD
chemokine
macrophages
uremic cardiomyopathy
Urology & Nephrology
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2022-01-28