Differential effects of vitamin D analogs on vascular calcification
Differential effects of vitamin D analogs on vascular calcification
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DOI：
10.1359/jbmr.070305
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发表时间：
2007-06-01
影响因子：
6.2
通讯作者：
Valdivielso, Jose M.
中科院分区：
文献类型：
--
作者：
Cardus, Anna;Panizo, Sara;Valdivielso, Jose M.
我们测试了骨化三醇及其类似物帕立骨化醇在体外和体内对VSMC钙化的影响。出于这个原因，细胞和动物与六分之五肾切除治疗与两种化合物。骨化三醇（而非帕立骨化醇）在体外和体内增加VSMC钙化，与钙和磷酸盐水平无关。这种钙化的增加是平行的RANKL/OPG ratio.Introduction的增加：血管钙化是终末期肾病患者的常见发现。此外，这些患者经常出现继发性甲状旁腺功能亢进，部分原因是肾脏骨化三醇合成减少。因此，主要的治疗选择之一是用骨化三醇或类似物治疗这些患者。然而，这种治疗提出了不必要的副作用，如增加血管calcium.Materials和方法：我们测试了骨化三醇及其类似物之一，帕立骨化醇，在体外和体内的终末期肾病动物的血管平滑肌细胞（VSMC）钙化的影响。当细胞与帕立骨化醇一起孵育时，不存在该效应。此外，只有与骨化三醇孵育的细胞显示RANKL/骨保护素（OPG）表达增加。接受高钙剂量骨化三醇和帕立骨化醇治疗的肾衰竭动物显示收缩压升高。然而，舒张压仅在帕立骨化醇给药的动物中显著升高。这种作用导致用骨化三醇治疗的动物的脉压显著增加。脉压增加可能是由骨化三醇治疗动物动脉中观察到的广泛钙化引起的。尽管与骨化三醇给药动物的血清钙和磷水平相似，但在帕立骨化醇给药动物的动脉中未观察到钙化增加。此外，血清甲状旁腺激素水平的下降是相似的，在两个treatment.Conclusions：我们得出结论，帕立骨化醇有不同的效果比骨化三醇在VSMC钙化，这可以解释在临床环境中观察到的差异的一部分。
We tested the effects of calcitriol and its analog paricalcitol on VSMC calcification in vitro and in vivo. For that reason, cells and animals with five-sixths nephrectomy were treated with both compounds. Calcitriol, but not paricalcitol, increased VSMC calcification in vitro and in vivo independently of calcium and phosphate levels. This increase in calcification was parallel to an increase in the RANKL/OPG ratio.Introduction: Vascular calcification is a common finding in patients with endstage renal disease. Furthermore, those patients often present secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Thus, one of the main therapeutic options is to treat those patients with calcitriol or analogs. However, this treatment presents unwanted side effects, such as increases in vascular calcification.Materials and Methods: We tested the effect on vascular smooth muscle cell (VSMC) calcification of calcitriol and one of its analogs, paricalcitol, in vitro and in vivo in animals with endstage renal disease.Results: Calcitriol increased calcification of VSMCs cultured in calcification media. This effect was not present when cells were incubated with paricalcitol. Furthermore, only cells incubated with calcitriol showed an increased RANKL/osteoprotegerin (OPG) expression. Animals with renal failure treated with hypercalcemic doses of calcitriol and paricalcitol showed an increase in systolic blood pressure. However, diastolic blood pressure only raised significantly in those animals treated with paricalcitol. This effect led to a significant increase in pulse pressure in animals treated with calcitriol. The increase in pulse pressure was likely caused by the extensive calcification observed in arteries of animals treated with calcitriol. This increase in calcification was not seen in arteries of animals treated with paricalcitol, despite having similar levels of serum calcium and phosphorus as animals treated with calcitriol. Furthermore, the decreases in serum PTH levels were similar in both treatments.Conclusions: We conclude that paricalcitol has a different effect than calcitriol in VSMC calcification and that this could explain part of the differences observed in the clinical settings.