Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways
Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways
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DOI：
10.1152/ajprenal.00406.2006
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发表时间：
2007-04-01
影响因子：
4.2
通讯作者：
Benchetrit, Sydney
中科院分区：
文献类型：
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作者：
Rashid, Gloria;Bernheim, Jacques;Benchetrit, Sydney
甲状旁腺激素（PTH）是主要的全身钙调节激素，与尿毒症血管改变有关。考虑到PTH可能对血管结构的有害作用，评估PTH对晚期糖基化终产物受体（RAGE）和白细胞介素6 (IL-6) mRNA和蛋白表达的影响似乎是合乎逻辑的，考虑到这些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。用10(-12)-10(-10)mol/l PTH刺激人脐静脉内皮细胞（HUVEC） 24 h。逆转录酶/PCR技术检测RAGE和IL-6 mRNA的表达。Western blot检测RAGE蛋白水平，ELISA检测IL-6分泌水平。我们评估了甲状旁腺素可能影响HUVEC功能的途径。PTH (10（-11)-10(-10) mol/l）显著增加RAGE mRNA和蛋白的表达。甲状旁腺激素也显著增加了IL-6 mRNA的表达，但蛋白水平没有变化。添加蛋白激酶（PKC或PKA）抑制剂或一氧化氮（NO）合成酶抑制剂可显著降低RAGE和IL-6 mRNA表达及RAGE蛋白表达。PTH刺激RAGE、IL-6 mRNA表达及RAGE蛋白表达。这些刺激作用可能通过PKC和PKA途径，也依赖于NO。这些数据可以解释甲状旁腺激素对动脉粥样硬化和动脉硬化进展的可能影响。
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.