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首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Long Term Effect of High Glucose and Phosphate Levels on the OPG/RANK/RANKL/TRAIL System in the Progression of Vascular Calcification in rat Aortic Smooth Muscle Cells
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Long Term Effect of High Glucose and Phosphate Levels on the OPG/RANK/RANKL/TRAIL System in the Progression of Vascular Calcification in rat Aortic Smooth Muscle Cells

机译：高葡萄糖和磷酸盐水平对大鼠主动脉平滑肌细胞血管钙化进程中OPG / RANK / RANKL / TRAIL系统的长期影响

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Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK) axis, and TNF-related apoptosis-inducing ligand (TRAIL) participate in vascular calcification process including atherosclerosis, but their contributions under high glucose (HG) and phosphate (HP) condition for a long-term period (more than 2 weeks) have not been fully determined. In this study, we evaluated the effects of HG and HP levels over 2 or 4 weeks on the progression of vascular calcification in rat vascular smooth muscle cells (VSMCs). Calcium deposition in VSMCs was increased in medium containing HG (30 mmol/L D-glucose) with β-glycerophosphate (β-GP, 12 mmol/L) after 2 weeks and increased further after 4 weeks. OPG mRNA and protein expressions were unchanged in HG group with or without β-GP after 2 weeks. However, after 4 weeks, OPG mRNA and protein expressions were significantly lower in HG group with β-GP. No significant expression changes were observed in RANKL, RANK, or TRAIL during the experiment. After 4 weeks of treatment in HG group containing β-GP and rhBMP-7, an inhibitor of vascular calcification, OPG expressions were maintained. Furthermore, mRNA expression of alkaline phosphatase (ALP), a marker of vascular mineralization, was lower in the presence of rhBMP-7. These results suggest that low OPG levels after long term HG and phosphate stimulation might reduce the binding of OPG to RANKL and TRAIL, and these changes could increase osteo-inductive VSMC differentiation, especially vascular mineralization reflected by increased ALP activity during vascular calcification.
机译：骨保护素（OPG），NF-κB配体的受体激活剂（RANKL）/NF-κB受体的激活剂（RANK）轴和TNF相关的凋亡诱导配体（TRAIL）参与了血管钙化过程，包括动脉粥样硬化，但在长期（超过2周）的高葡萄糖（HG）和磷酸盐（HP）状况尚未完全确定。在这项研究中，我们评估了2到4周内HG和HP水平对大鼠血管平滑肌细胞（VSMC）血管钙化进展的影响。 2周后，含HG（30 mmol / L D-葡萄糖）和β-甘油磷酸酯（β-GP，12 mmol / L）的培养基中VSMC中的钙沉积增加，而4周后进一步增加。有或无β-GP的HG组2周后OPG mRNA和蛋白表达均未改变。然而，在4周后，β-GP的HG组的OPG mRNA和蛋白表达显着降低。在实验期间，在RANKL，RANK或TRAIL中未观察到明显的表达变化。在含有β-GP和rhBMP-7（血管钙化抑制剂）的HG组中治疗4周后，OPG的表达得以维持。此外，在存在rhBMP-7的情况下，碱性磷酸酶（ALP）（一种血管矿化的标志物）的mRNA表达较低。这些结果表明，长期HG和磷酸盐刺激后较低的OPG水平可能会降低OPG与RANKL和TRAIL的结合，这些变化可能会增加骨诱导性VSMC分化，尤其是血管钙化过程中ALP活性增加所反映的血管矿化。

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