کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5951010 | 1172407 | 2009 | 8 صفحه PDF | دانلود رایگان |

ObjectiveSecondary hyperparathyroidism of chronic kidney disease promotes vascular calcification. Calcimimetics reduce serum parathyroid hormone, calcium (Ca), and phosphorus by calcium-sensing receptor (CaR) activation. Here we examined possible effects of the calcimimetic R-568 (R-568) on the progression of aortic calcification and atherosclerosis in apoEâ/â mice with chronic renal failure (CRF) and the potential implication of aortic smooth muscle cell CaR.Methods and resultsApoEâ/â mice were assigned to 3 CRF groups and 1 non-CRF group receiving daily gavage with R-568, calcitriol, or vehicle. Serum Ca and phosphorus and parathyroid gland volume of CRF mice were decreased by R-568, whereas elevated serum FGF23 and total cholesterol remained unchanged. Both aortic plaque and non-plaque calcification was lower in R-568 mice, and so was atherosclerotic plaque area fraction. In vitro, R-568 induced a decrease in smooth muscle cell calcification when cultured in high phosphate medium. This decrease was abolished in CaR-SiRNA-transfected cells.ConclusionsThe calcimimetic R-568 delayed the progression of both aortic calcification and atherosclerosis in uremic apoEâ/â mice. This effect was mediated via a better control of hyperparathyroidism including serum Ca and phosphorus. Direct vascular CaR activation also could have played a role in the observed effects.
Journal: Atherosclerosis - Volume 205, Issue 1, July 2009, Pages 55-62