The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification.
The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification.
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DOI：
10.3389/fgene.2013.00004
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发表时间：
2013
影响因子：
3.7
通讯作者：
Martin L
中科院分区：
文献类型：
--
作者：
Lefthériotis G;Omarjee L;Le Saux O;Henrion D;Abraham P;Prunier F;Willoteaux S;Martin L
血管钙化是一个复杂的动态过程，发生在各种生理条件下，如衰老和运动或获得性代谢紊乱，如糖尿病或慢性肾功能不全。在几种遗传性疾病中也观察到动脉钙化，揭示了不平衡或有缺陷的抗钙化因子或促钙化因子的重要作用。弹性假黄瘤（PXE）是一种遗传性疾病（OMIM 264800），其特征是各种软结膜组织（包括皮肤、眼睛和动脉介质）中的弹性纤维断裂和钙化。PXE病是由ABCC6基因突变引起的，ABCC6基因编码一种主要在肝、肾中表达的ATP结合盒转运蛋白，这表明它是一种遗传起源的原型代谢性软组织钙化病。PXE动脉疾病的临床表现特征为冠状动脉（心肌梗死）、脑动脉（动脉瘤和中风）和下肢外周动脉疾病的风险增加。然而，动脉壁的结构和功能的变化引起的PXE仍然无法解释。使用的重组小鼠模型灭活的Abcc6基因是一个重要的工具，了解PXE的病理生理学，虽然在这个模型中的血管影响仍然有限的日期。PXE与其他遗传性钙化病表型的重叠可能为我们理解PXE病提供重要信息。
Vascular calcification is a complex and dynamic process occurring in various physiological conditions such as aging and exercise or in acquired metabolic disorders like diabetes or chronic renal insufficiency. Arterial calcifications are also observed in several genetic diseases revealing the important role of unbalanced or defective anti- or pro-calcifying factors. Pseudoxanthoma elasticum (PXE) is an inherited disease (OMIM 264800) characterized by elastic fiber fragmentation and calcification in various soft conjunctive tissues including the skin, eyes, and arterial media. The PXE disease results from mutations in the ABCC6 gene, encoding an ATP-binding cassette transporter primarily expressed in the liver, kidneys suggesting that it is a prototypic metabolic soft-tissue calcifying disease of genetic origin. The clinical expression of the PXE arterial disease is characterized by an increased risk for coronary (myocardial infarction), cerebral (aneurysm and stroke), and lower limb peripheral artery disease. However, the structural and functional changes in the arterial wall induced by PXE are still unexplained. The use of a recombinant mouse model inactivated for the Abcc6 gene is an important tool for the understanding of the PXE pathophysiology although the vascular impact in this model remains limited to date. Overlapping of the PXE phenotype with other inherited calcifying diseases could bring important informations to our comprehension of the PXE disease.