Apelin: A novel inhibitor of vascular calcification in chronic kidney disease
Apelin: A novel inhibitor of vascular calcification in chronic kidney disease
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DOI：
10.1016/j.atherosclerosis.2015.10.102
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发表时间：
2016-01-01
期刊：
影响因子：
5.3
通讯作者：
Liu, Wen-Hu
中科院分区：
文献类型：
--
作者：
Han, Xue;Wang, Li-Yan;Liu, Wen-Hu
背景：血管钙化（VC）与慢性肾脏疾病（CKD）的心血管事件密切相关。Apelin是一种有效的心血管功能调节剂，但其在CKD期间VC中的作用尚不清楚。我们确定了apelin是否在磷酸盐诱导的人主动脉平滑肌细胞矿化（HASMCs）和腺嘌呤诱导的CKD大鼠主动脉钙化中起作用。方法与结果：体外发现Apelin -13抑制HASMCs钙沉积(Pi(+) Apelin（+）组vs Pi(+) Apelin（-）组：50.1 +/- 6.21 ug/mg vs 146.67 +/- 10.02 ug/mg蛋白，p = 0.012)，抑制成骨转化基因BMP-2、骨保护素（OPG）和Cbfa1的诱导。这种作用是通过干扰钠依赖性磷酸盐共转运蛋白（Pit-1）的表达和磷酸盐摄取来介导的。在体内，腺嘌呤诱导的CKD高磷血症大鼠（腺嘌呤（+）apelin(-) vs对照：0.37 +/- 0.09 ng/ml vs 0.68 +/- 0.16 ng/ml, p = 0.003）血浆APJ水平降低（腺嘌呤（+）apelin(-) vs对照：6.91 +/- 0.23 mmoL/L vs 2.3 +/- 0.07 mmoL/L, p = 0.001）和主动脉钙化。外源性补充apelin- 13使apelin/APJ系统水平正常化，显著改善主动脉钙化，并抑制Runx2、OPG和Pit-1的表达。结论：Apelin通过下调Pit-1表达抑制VSMCs成骨分化，从而改善VC。提示apelin在CKD的VC治疗中具有潜在的治疗价值。2015爱思唯尔爱尔兰有限公司版权所有。
Background: Vascular calcification (VC) is closely related to cardiovascular events in chronic kidney disease (CKD). Apelin has emerged as a potent regulator of cardiovascular function, but its role in VC during CKD remains unknown. We determined whether apelin plays a role in phosphate-induced mineralization of human aortic smooth muscle cells (HASMCs) and in adenine-induced CKD rats with aortic calcification.Methods and results: In vitro, apelin-13 was found to inhibit calcium deposition in HASMCs (Pi(+) Apelin(+) group vs Pi(+) Apelin(-) group: 50.1 +/- 6.21 ug/mg vs 146.67 +/- 10.02 ug/mg protein, p = 0.012) and to suppress the induction of the osteoblastic transformation genes BMP-2, osteoprotegerin (OPG) and Cbfa1. This effect was mediated by interference of the sodium-dependent phosphate cotransporter (Pit-1) expression and phosphate uptake. In vivo, decreased plasma apelin levels (adenine(+) apelin(-) vs vehicle: 0.37 +/- 0.09 ng/ml vs 0.68 +/- 0.16 ng/ml, p = 0.003) and downregulation of APJ in the aorta were found in adenine-induced CKD rats with hyperphosphatemia (adenine(+) apelin(-) vs vehicle: 6.91 +/- 0.23 mmoL/L vs 2.3 +/- 0.07 mmoL/L, p = 0.001) and aortic calcification. Exogenous supplementation of apelin- 13 normalized the level of the apelin/APJ system and significantly ameliorated aortic calcification, as well as the suppression of Runx2, OPG and Pit-1 expression.Conclusions: Apelin ameliorates VC by suppressing osteoblastic differentiation of VSMCs through downregulation of Pit-1. These results suggest apelin may have potential therapeutic value for treatment of VC in CKD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.