Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism
Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism
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DOI：
10.1093/ndt/gfk008
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发表时间：
2006-04-01
影响因子：
6.1
通讯作者：
Akizawa, T
中科院分区：
文献类型：
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作者：
Mizobuchi, M;Ogata, H;Akizawa, T
背景资料。心血管疾病是终末期肾病(ESKD)患者最常见的死亡原因。血管钙化在普通人群中是心血管事件的确认危险因素，在ESKD患者中发生率较高。尽管血管钙化在ESKD中的发病率很高，但其发病机制仍不清楚。本研究检测了重度继发性甲状旁腺功能亢进(SHPT)肾大部切除大鼠钙化动脉中骨相关因子的表达。将7周龄雄性SD大鼠随机分为5组：假手术组，给予正常饲料[磷(P)0.8%，钙(Ca)1.1%](Sham)；假手术组，给予高磷低钙(HPLCa)饲料(1.2%磷，0.4%钙)(Sham+HPLCa)；5/6肾切除大鼠，给予正常饲料(NX)；5/6肾切除和甲状旁腺切除大鼠，给予HPLCa饲料(NX+PTX+HPLCa)。每组喂养时间均为10周。然后处死大鼠，并检测它们的血清。采用实时定量逆转录聚合酶链式反应(Real-time PCR)检测腹主动脉上段核心结合因子α1(Cbfa1)和钠依赖磷酸共转运体(Pit-1)基因的表达。用von Kossa染色检查下半部分的钙化情况。NX+HPLCa组血清P水平和Cax-P乘积均显著高于其他组。NX+HPLCa组也出现严重的甲状旁腺功能亢进。NX+HPLCa组仅见中层血管钙化。NX+HPLCa组大鼠主动脉中Cbfa1和Pit-1mRNA的表达水平明显高于其他组。这些结果提示，Cbfa1和Pit-1可能是导致严重高磷血症和SHPT的尿毒症大鼠中层血管钙化的部分原因。
Background. Cardiovascular disease is the most frequent cause of death in patients with end-stage kidney disease (ESKD). Vascular calcification is a confirmed risk factor for cardiovascular events in the general population and has a high occurrence in patients with ESKD. Despite the high prevalence of vascular calcification in ESKD, the pathogenesis of the disorder is still obscure. The present study examined the expressions of bone-associated factors in calcified arteries in subtotally nephrectomized rats with severe secondary hyperparathyroidism (SHPT).Methods. Seven-week-old male Sprague-Dawley rats were divided into five groups as follows: sham-operated rats that received a normal diet [0.8% of phosphorus (P), 1.1% of calcium (Ca)] (Sham), sham-operated rats that received a high-phosphorus and low-calcium (HPLCa) diet (1.2% P, 0.4% Ca) (Sham+HPLCa), 5/6 nephrectomized rats that received a normal diet as the uraemic control group (Nx), and 5/6 nephrectomized rats that received a HPLCa diet to induce the development of SHPT (Nx+HPLCa), and 5/6 nephrectomized and parathyroidectomized rats that received a HPLCa diet (Nx+PTx+HPLCa). The feeding period of each group was 10 weeks. The rats were then sacrificed and their serum was examined. The upper part of the abdominal aorta was used to investigate the expression of mRNAs of core-binding factor alpha-1 (Cbfa1) and sodium-dependent phosphate cotransporter (Pit-1) by real-time reverse transcriptase polymerase chain reaction (real-time PCR) analysis. The lower part was examined for calcification by von Kossa staining.Results. Serum P level and Ca x P products increased significantly in the Nx+HPLCa group compared with those of any other groups. Severe hyperparathyroidism was also observed in the Nx+HPLCa group. Vascular calcification (medial layer) was observed in the Nx+HPLCa group only. There was a significant increase in Cbfa1 and Pit-1 mRNA expression levels in the aorta of the Nx+HPLCa group compared with that of any other groups.Conclusions. These results suggest that medial layer vascular calcification in uraemic rats with severe hyperphosphataemia and SHPT may be caused in part by Cbfa1 and Pit-1.