Cardús Anna, Panizo Sara, Parisi Eva, Fernandez Elvira, Valdivielso Jose M
Department of Medicine, University of Lleida, Lleida, Spain.
J Bone Miner Res. 2007 Jun;22(6):860-6. doi: 10.1359/jbmr.070305.
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.
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.
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.
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.
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.
我们在体外和体内测试了骨化三醇及其类似物帕立骨化醇对血管平滑肌细胞（VSMC）钙化的影响。因此，对行五分之六肾切除术的细胞和动物使用这两种化合物进行处理。骨化三醇而非帕立骨化醇，在体外和体内均独立于钙和磷水平增加了VSMC钙化。这种钙化增加与核因子κB受体活化因子配体（RANKL）/骨保护素（OPG）比值的增加平行。
血管钙化在终末期肾病患者中很常见。此外，这些患者常出现继发性甲状旁腺功能亢进，部分原因是肾脏中骨化三醇合成减少。因此，主要的治疗选择之一是用骨化三醇或其类似物治疗这些患者。然而，这种治疗存在不良副作用，如血管钙化增加。
我们在终末期肾病动物的体外和体内测试了骨化三醇及其类似物之一帕立骨化醇对血管平滑肌细胞（VSMC）钙化的影响。
骨化三醇增加了在钙化培养基中培养的VSMC的钙化。当细胞与帕立骨化醇孵育时，这种作用不存在。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。用高钙血症剂量的骨化三醇和帕立骨化醇治疗的肾衰竭动物收缩压升高。然而，舒张压仅在接受帕立骨化醇治疗的动物中显著升高。这种作用导致接受骨化三醇治疗的动物脉压显著增加。脉压增加可能是由于在接受骨化三醇治疗的动物动脉中观察到广泛的钙化。尽管接受帕立骨化醇治疗的动物血清钙和磷水平与接受骨化三醇治疗的动物相似，但在其动脉中未观察到这种钙化增加。此外，两种治疗中血清甲状旁腺激素（PTH）水平的降低相似。
我们得出结论，帕立骨化醇在VSMC钙化方面具有与骨化三醇不同的作用，这可以解释在临床环境中观察到的部分差异。
