Vascular calcification is dependent on plasma levels of pyrophosphate.
Vascular calcification is dependent on plasma levels of pyrophosphate.
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DOI：
10.1038/ki.2013.521
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发表时间：
2014-06
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
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终末期肾病患者血浆焦磷酸盐（血管钙化的内源性抑制剂）水平降低，并与动脉钙化呈负相关。然而，目前尚不清楚低血浆水平是否直接致病，或者仅仅是组织水平降低的标志物。这是在一个动物模型中进行测试的，在该模型中，将Ectas移植到正常小鼠和缺乏外核苷酸焦磷酸酶磷酸二酯酶（释放细胞外焦磷酸的酶）的Enpp1 −/−小鼠之间。Enpp1 −/−小鼠的血浆焦磷酸盐水平非常低，2个月后出现主动脉钙化，高磷酸盐饮食大大加速了钙化。Enpp1 −/−小鼠的主动脉在移植到喂食高磷酸盐饮食的野生型小鼠体内后没有进一步钙化。野生型小鼠的同种异体主动脉移植物在Enpp1 −/−小鼠中钙化，但比相邻的受体Enpp1 −/−主动脉钙化少。在野生型和Enpp 1 −/−小鼠之间的移植中，供体和受体主动脉钙含量没有差异，表明移植本身不影响钙化。组织学检查显示中膜钙化，无排斥反应迹象。因此，正常水平的细胞外焦磷酸盐足以防止血管钙化，尽管正常的血管细胞外焦磷酸盐产生，但全身性Enpp1缺乏足以产生血管钙化。这确立了循环细胞外焦磷酸盐在预防血管钙化中的重要作用。
Plasma levels of pyrophosphate, an endogenous inhibitor of vascular calcification, are reduced in end-stage renal disease and correlate inversely with arterial calcification. However, it is not known whether the low plasma levels are directly pathogenic or are merely a marker of reduced tissue levels. This was tested in an animal model in which aortas were transplanted between normal mice and Enpp1−/− mice lacking ectonucleotide pyrophosphatase phosphodiesterase, the enzyme that releases extracellular pyrophosphate. Enpp1−/− mice had very low plasma pyrophosphate and developed aortic calcification by 2 months that was greatly accelerated with a high-phosphate diet. Aortas of Enpp1−/− mice showed no further calcification after transplantation into wild type mice fed a high phosphate diet. Aorta allografts of wild type mice calcified in Enpp1−/− mice but less so than the adjacent recipient Enpp1−/− aorta. Donor and recipient aortic calcium contents did not differ in transplants between wild type and Enpp1−/− mice, demonstrating that transplantation per se did not affect calcification. Histology revealed medial calcification with no signs of rejection. Thus, normal levels of extracellular pyrophosphate are sufficient to prevent vascular calcification and systemic Enpp1 deficiency is sufficient to produce vascular calcification despite normal vascular extracellular pyrophosphate production. This establishes an important role for circulating extracellular pyrophosphate in preventing vascular calcification.
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影响因子：
19.6
作者：
Lomashvili, Koba A.;Monier-Faugere, Marie-Claude;Wang, Xiaonan;Malluche, Hartmut H.;O'Neill, W. Charles
通讯作者：
O'Neill, W. Charles
影响因子：
6.1
作者：
Riser, Bruce L.;Barreto, Fellype Carvalho;Massy, Ziad A.
通讯作者：
Massy, Ziad A.
影响因子：
64.8
作者：
FLEISCH, H;RUSSEL, RGG;STRAUMANN, F
通讯作者：
STRAUMANN, F
影响因子：
15.9
作者：
RUSSELL, RGG;BISAZ, S;FLEISCH, H
通讯作者：
FLEISCH, H
影响因子：
13.6
作者：
Lomashvili, KA;Khawandi, W;O'Neill, WC
通讯作者：
O'Neill, WC