ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy.
ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy.
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DOI：
10.1038/ncomms10006
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发表时间：
2015-12-01
影响因子：
16.6
通讯作者：
Braddock DT
中科院分区：
文献类型：
--
作者：
Albright RA;Stabach P;Cao W;Kavanagh D;Mullen I;Braddock AA;Covo MS;Tehan M;Yang G;Cheng Z;Bouchard K;Yu ZX;Thorn S;Wang X;Folta-Stogniew EJ;Negrete A;Sinusas AJ;Shiloach J;Zubal G;Madri JA;De La Cruz EM;Braddock DT
血管壁异位钙化的疾病从婴儿全身性动脉钙化(GACI)等致命的孤儿疾病到与衰老相关的动脉硬化和慢性肾脏疾病(CKD)的钙化等常见疾病。GACI是一种致命的孤儿疾病，婴儿在出生时中、大动脉内弹力板钙化，心力衰竭消失，而CKD的钙化是肾功能衰竭患者普遍存在的血管钙化。这两种疾病的特征都是血管性Mönckeburg硬化症，并伴有血浆无机焦磷酸(PPI)浓度降低。在这里，我们证明了皮下注射ENPP1-Fc融合蛋白可以预防GACI动物模型中的死亡率、血管钙化和疾病后遗症，并伴随着完整的临床和生物标记物反应。我们的发现对治疗罕见和常见病的异位血管钙化有一定的指导意义。婴儿期全身性动脉钙化(GACI)是由ENPP1酶缺陷引起的终末性疾病。在这里，Albrigh等人。结果表明，ENPP1酶替代疗法可以防止GACI小鼠的异位钙化和死亡率，这表明这是一种治疗人类血管钙化的新方法。
Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Mönckeburg's sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PPi). Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. Our findings have implications for the treatment of rare and common diseases of ectopic vascular calcification. Generalized arterial calcification of infancy (GACI) is a terminal disease caused by the ENPP1 enzyme deficiency. Here, Albrigh et al. show that ENPP1 enzyme replacement therapy prevents the ectopic calcifications and mortality in mice with GACI, suggesting a novel treatment for vascular calcification in humans.