Rashid Gloria, Bernheim Jacques, Green Janice, Benchetrit Sydney
Dept. of Nephrology and Hypertension, Meir Medical Center, Tchernichovsky 59, Kfar-Saba 44281, Israel.
Am J Physiol Renal Physiol. 2007 Apr;292(4):F1215-8. doi: 10.1152/ajprenal.00406.2006. Epub 2006 Dec 26.
Parathyroid hormone (PTH), the major systemic calcium-regulating hormone, has been linked to uremic vascular changes. Considering the possible deleterious action of PTH on vascular structures, it seemed logical to evaluate the impact of PTH on the receptor of advanced glycation end products (RAGE) and interleukin 6 (IL-6) mRNA and protein expression, taking into account that such parameters might be involved in the pathogenesis of vascular calcification, atherosclerosis, and/or arteriolosclerosis. Human umbilical vein cord endothelial cells (HUVEC) were stimulated for 24 h with 10(-12)-10(-10) mol/l PTH. The mRNA expression of RAGE and IL-6 was established by reverse transcriptase/PCR techniques. RAGE protein levels were determined by Western blot and IL-6 secretion was measured by ELISA. The pathways by which PTH may have an effect on HUVEC functions were evaluated. PTH (10(-11)-10(-10)mol/l) significantly increased RAGE mRNA and protein expression. PTH also significantly increased IL-6 mRNA expression without changes at protein levels. The addition of protein kinase (PKC or PKA) inhibitors or nitric oxide (NO) synthase inhibitors significantly reduced the RAGE and IL-6 mRNA expression and the RAGE protein expression. PTH stimulates the mRNA expressions of RAGE and IL-6 and the protein expression of RAGE. These stimulatory effects are probably through PKC and PKA pathways and are also NO dependent. Such data may explain the possible impact of PTH on the atherosclerotic and arteriosclerotic progression.
甲状旁腺激素（PTH）是调节全身钙水平的主要激素，与尿毒症血管变化有关。考虑到PTH对血管结构可能存在有害作用，鉴于晚期糖基化终产物受体（RAGE）和白细胞介素6（IL-6）的mRNA及蛋白表达参数可能参与血管钙化、动脉粥样硬化和/或小动脉硬化的发病机制，评估PTH对其的影响似乎是合理的。用人脐静脉内皮细胞（HUVEC）以10(-12)-10(-10)mol/L的PTH刺激24小时。通过逆转录酶/聚合酶链反应（RT/PCR）技术检测RAGE和IL-6的mRNA表达。通过蛋白质印迹法测定RAGE蛋白水平，采用酶联免疫吸附测定法（ELISA）检测IL-6分泌。评估了PTH可能影响HUVEC功能的途径。PTH（10(-11)-10(-10)mol/L）显著增加RAGE的mRNA和蛋白表达。PTH也显著增加IL-6的mRNA表达，但蛋白水平无变化。添加蛋白激酶（PKC或PKA）抑制剂或一氧化氮（NO）合酶抑制剂可显著降低RAGE和IL-6的mRNA表达以及RAGE蛋白表达。PTH刺激RAGE和IL-6的mRNA表达以及RAGE的蛋白表达。这些刺激作用可能通过PKC和PKA途径，且也依赖于NO。这些数据可能解释了PTH对动脉粥样硬化和小动脉硬化进展的潜在影响。
