Activation of nuclear factor-kappa B accelerates vascular calcification by inhibiting ankylosis protein homolog expression.
Activation of nuclear factor-kappa B accelerates vascular calcification by inhibiting ankylosis protein homolog expression.
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DOI：
10.1038/ki.2012.40
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发表时间：
2012-07
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
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血管钙化是心血管死亡的主要危险因素，特别是对于终末期肾病和糖尿病患者。虽然慢性炎症是病因之一，但其潜在机制尚不完全清楚。为了阐明这一点，我们研究了核因子-κ B（NF-κB）诱导，炎症介质，如何可能促进血管钙化。肿瘤坏死因子（TNF）激活NF-κB促进无机磷酸盐诱导的人主动脉平滑肌细胞钙化焦磷酸盐（钙化抑制剂）流出到细胞外基质被抑制沿着强直蛋白同源物（ANKH）的表达减少，ANKH是一种控制细胞焦磷酸盐流出的跨膜蛋白。这些细胞中ANKH表达的恢复克服了焦磷酸盐流出和钙化的减少。Tristetraprolin是NF-κB激活的下游产物，可能介导ANKH mRNA的不稳定，因为其被shRNA敲低增加ANKH表达并减少钙化。慢性肾功能衰竭模型大鼠血清TNF水平升高，NF-κB活化，ANKH水平降低。相反，抑制NF-κB可维持ANKH的表达，并减轻体内和体外血管钙化。人钙化的动脉粥样硬化病变和慢性肾病患者的动脉都有NF-κB活化和ANKH表达降低。因此，TNF激活的NF-κB通过抑制强直蛋白同源物表达和随后的焦磷酸盐分泌促进炎症加速的血管钙化。
Vascular calcification is a major risk factor of cardiovascular mortality, particularly for patients with end-stage renal disease and diabetes. Although chronic inflammation is one of the etiologic factors, the underlying mechanism is not fully understood. To clarify this, we studied how nuclear factor-kappa B (NF-κB) induction, a mediator of inflammation, might promote vascular calcification. Activation of NF-κB by tumor necrosis factor (TNF) promoted inorganic phosphate-induced calcification in human aortic smooth muscle cells. Pyrophosphate (an inhibitor of calcification) efflux to the extracellular matrix was suppressed along with the decreased expression of ankylosis protein homolog (ANKH), a transmembrane protein that controls pyrophosphate efflux of cells. The restoration of ANKH expression in these cells overcame the decreased pyrophosphate efflux and calcification. Tristetraprolin, a downstream product of NF-κB activation, may mediate destablization of ANKH mRNA since its knockdown by shRNA increased ANKH expression and decreased calcification. Furthermore, a rat chronic renal failure model, with increased serum TNF levels, activated NF-κB and decreased ANKH levels. In contrast, the inhibition of NF-κB maintained ANKH expression and attenuated vascular calcification both in vivo and in vitro. Both human calcified atherosclerotic lesions and arteries from patients with chronic kidney disease had activated NF-κB and decreased ANKH expression. Thus, TNF-activated NF-κB promotes inflammation-accelerated vascular calcification by inhibiting ankylosis protein homolog expression and consequent pyrophosphate secretion.
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影响因子：
6.1
作者：
Guérin, AP;London, GM;Metivier, F
通讯作者：
Metivier, F
影响因子：
4.8
作者：
Byon, Chang Hyun;Javed, Amjad;Chen, Yabing
通讯作者：
Chen, Yabing
影响因子：
82.9
作者：
Park, Bae Keun;Zhang, Honglai;Wang, Cun-Yu
通讯作者：
Wang, Cun-Yu
DOI：
10.1161/atvbaha.107.153668
发表时间：
2007-12-01
影响因子：
8.7
作者：
Al-Aly, Ziyad;Shao, Jian-Su;Towler, Dwight A.
通讯作者：
Towler, Dwight A.
DOI：
10.1161/hypertensionaha.109.134205
发表时间：
2010-03
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Shao JS;Cheng SL;Sadhu J;Towler DA
通讯作者：
Towler DA