Moderate kidney disease inhibits atherosclerosis regression
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Updated: Jun 18, 2026
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Manish P Ponda1, Irina Barash, Jonathan E Feig
1Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10065, United States. mponda@rockefeller.edu
Insights
Chronic kidney disease hinders atherosclerosis regression, increasing cardiovascular risk. Impaired chemokine receptor 7 (CCR7) signaling in macrophages may explain this effect in kidney disease patients.
Area of Science:
- Cardiovascular Research
- Nephrology
- Immunology
Background:
- Chronic kidney disease (CKD) is linked to accelerated cardiovascular disease.
- The precise mechanisms behind this increased cardiovascular risk in CKD remain unclear.
- Impaired atherosclerosis regression is a potential, uninvestigated factor.
Purpose of the Study:
- To investigate if impaired atherosclerosis regression in renal disease is a novel risk factor for CKD patients.
- To explore the role of macrophage migration and signaling in this process.
Main Methods:
- A mouse transplant model was used to study atherosclerosis regression.
- Atheromatous aortic segments from Apolipoprotein E knock-out mice were transplanted into control or uremic wild-type mice.
- Macrophage presence and gene expression (CCR7, SRF) within lesions were analyzed.
Main Results:
- Atherosclerotic lesions regressed by 55% in control mice but increased by 17% in uremic mice (p<0.01).
- Lesions in uremic mice showed significantly higher macrophage accumulation (36,300 µm² vs. 12,600 µm², p<0.01).
- Despite CCR7 upregulation, gene expression indicated impaired CCR7 signaling due to down-regulated SRF target genes in uremic macrophages.
Conclusions:
- Moderate kidney disease inhibits atherosclerosis regression in a mouse model.
- Impaired CCR7 signaling in macrophages is a potential mechanism contributing to inhibited regression in CKD.
Unlabelled:
Chronic kidney disease (CKD) accelerates cardiovascular disease. The mechanisms that explain this independent, excess risk associated with CKD have not been fully elucidated.
Objectives:
We propose that impaired regression of atherosclerosis in renal disease represents a novel risk factor for the heightened morbidity and mortality and resistance to treatment observed in patients with CKD.
Methods And Results:
Using a transplant model to study atherosclerosis regression, we transplanted atheromatous aortic segments generated in Apolipoprotein E knock-out (ApoE(-/-)) mice, into either control or moderately uremic, normolipidemic, wild-type mice. In non-uremic mice, lesions regressed 55%, whereas lesions in uremic mice increased in size by 17% (p<0.01 for control vs. uremic). The lesions in uremic mice were also characterized by a greater presence of macrophages (36,300 microm(2) vs. 12,600 microm(2), p<0.01). This finding was despite upregulation of chemokine receptor 7 (CCR7), normally a migration factor, in uremic lesion macrophages. Gene expression analysis of lesion macrophages showed relative down-regulation of serum response factor (SRF) target genes in the uremic group, consistent with impaired CCR7 signaling.
Conclusion:
Moderate kidney disease inhibits regression of atherosclerosis in a mouse transplant model. This inhibition may be a result of impaired CCR7 signaling.
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