Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.
J Mol Med (Berl). 2010 May;88(5):467-75. doi: 10.1007/s00109-010-0596-3. Epub 2010 Feb 23.
Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic calcification of connective tissue in skin, Bruch's membrane of the eye, and walls of blood vessels. PXE is caused by mutations in the ABCC6 gene, but the exact etiology is still unknown. While observations on patients suggest that high calcium intake worsens the clinical symptoms, the patient organization PXE International has published the dietary advice to increase calcium intake in combination with increased magnesium intake. To obtain more data on this controversial issue, we examined the effect of dietary calcium and magnesium in the Abcc6(-/-) mouse, a PXE mouse model which mimics the clinical features of PXE. Abcc6(-/-) mice were placed on specific diets for 3, 7, and 12 months. Disease severity was measured by quantifying calcification of blood vessels in the kidney. Raising the calcium content in the diet from 0.5% to 2% did not change disease severity. In contrast, simultaneous increase of both calcium (from 0.5% to 2.0%) and magnesium (from 0.05% to 0.2%) slowed down the calcification significantly. Our present findings that increase in dietary magnesium reduces vascular calcification in a mouse model for PXE should stimulate further studies to establish a dietary intervention for PXE.
弹性假黄瘤(PXE)是一种遗传性疾病,其特征是结缔组织在皮肤、眼部的 Bruch 膜和血管壁中异位钙化。PXE 是由 ABCC6 基因突变引起的,但确切的病因仍不清楚。尽管对患者的观察表明高钙摄入会使临床症状恶化,但 PXE 国际患者组织已发表了增加钙摄入并结合增加镁摄入的饮食建议。为了获得更多关于这个有争议的问题的数据,我们研究了膳食钙和镁对 PXE 小鼠模型(Abcc6(-/-) 小鼠)的影响,该模型模拟了 PXE 的临床特征。Abcc6(-/-) 小鼠被置于特定的饮食中 3、7 和 12 个月。通过定量测量肾脏血管的钙化来衡量疾病的严重程度。将饮食中的钙含量从 0.5%提高到 2%并没有改变疾病的严重程度。相比之下,同时增加钙(从 0.5%增加到 2.0%)和镁(从 0.05%增加到 0.2%)显著减缓了钙化。我们目前的研究结果表明,增加膳食镁可以减少 PXE 小鼠模型中的血管钙化,这应该会刺激进一步的研究,以确定 PXE 的饮食干预措施。