Effects of calcimimetic on vascular calcification and atherosclerosis in uremic mice

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.