Related Experiment Video
Updated: Jun 24, 2026
Analysis of Extracellular Vesicle-Mediated Vascular Calcification Using In Vitro and In Vivo Models
Published on: January 27, 2023
Effects of calcimimetic on vascular calcification and atherosclerosis in uremic mice
Nobuhiko Joki1, Igor G Nikolov, Axelle Caudrillier
1Inserm Unit 845, Necker Hospital, University Paris 5, Paris, France. jokinobuhiko@gmail.com
Abstract:
Recent in vitro and in vivo studies suggest that the calcium-sensing receptor (CaR) plays a role in the process of vascular calcification. Whether it is also involved in the process of atherosclerosis remains an open issue. It is of interest to note that CaR expression is reduced in the arteries of uremic patients, compared with that of non-uremic subjects, and that the progression of vascular calcification in uremic patients is much faster than in general population. It is therefore important to identify treatments which allow us to slow this rapid progression. In this context, it was tempting to examine possible vascular effects of a calcimimetic in the setting of chronic kidney disease (CKD), all the more since cinacalcet, an allosteric modulator of the CaR, has been recently approved for the treatment of hyperparathyroidism secondary to CKD. We have therefore tested the effects of the calcimimetic R-568 in the experimental model of the uremic apoE(-/-) mouse. We have been able to demonstrate that this calcimimetic did not only delay the progression of aortic calcification, but also that of atherosclerosis. This beneficial effect might have occurred through systemic as well as direct local effects, probably via an activation of the CaR in vascular endothelial and smooth muscle cells. The present review is therefore devoted to the effects of calcimimetics on uremia-induced vascular disease.
Insights
Calcimimetics, drugs that activate the calcium-sensing receptor (CaR), show promise in treating vascular disease in chronic kidney disease (CKD) patients. Studies indicate these drugs can slow both vascular calcification and atherosclerosis progression.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Pharmacology
Background:
- The calcium-sensing receptor (CaR) is implicated in vascular calcification.
- CaR expression is reduced in uremic patients, correlating with accelerated vascular calcification.
- Atherosclerosis involvement with CaR remains unclear, necessitating investigation into therapeutic interventions.
Purpose of the Study:
- To investigate the vascular effects of calcimimetics in chronic kidney disease (CKD).
- To evaluate the efficacy of the calcimimetic R-568 in an experimental model of uremia.
- To determine if calcimimetics can mitigate vascular calcification and atherosclerosis progression in uremic conditions.
Main Methods:
- Utilized the uremic apoE(-/-) mouse model.
- Administered the calcimimetic R-568 to assess its impact on vascular disease progression.
- Examined effects on aortic calcification and atherosclerosis development.
Main Results:
- The calcimimetic R-568 significantly delayed the progression of aortic calcification.
- R-568 also demonstrated a delay in the progression of atherosclerosis.
- Beneficial effects may stem from systemic and local CaR activation in vascular cells.
Conclusions:
- Calcimimetics represent a potential therapeutic strategy for uremia-induced vascular disease.
- Targeting the CaR with calcimimetics may offer a dual benefit against calcification and atherosclerosis.
- Further research into calcimimetic mechanisms in CKD vascular complications is warranted.
