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交联弹性蛋白样多肽膜作为中层动脉钙化模型。

Cross-Linked Elastin-like Polypeptide Membranes as a Model for Medial Arterial Calcification.

机构信息

Department of Mining and Materials Engineering , McGill University , Montreal , Quebec H3A 0C5 , Canada.

Molecular Medicine , Hospital for Sick Children , Toronto , Ontario M5G 0A4 , Canada.

出版信息

Biomacromolecules. 2019 Jul 8;20(7):2625-2636. doi: 10.1021/acs.biomac.9b00417. Epub 2019 Jun 21.

Abstract

Calcium phosphate minerals deposit on the elastin-rich medial layers of arteries in the majority of seniors, diabetic, and chronic kidney disease patients, causing severe cardiovascular complications. There is no cure for medial calcification, and the mechanism of mineral formation on elastin layers is unknown. Here we propose cross-linked elastin-like polypeptide membranes as models to study medial calcification. Calcium phosphates deposit first on fibers and filaments and then spread to globular structures present in the membranes. Mineral phase evolution analyzed by near-edge X-ray spectroscopy matches that previously observed in a mouse model of medial calcification, showing that this simple system captures some of the key in vivo findings. This work shows how minerals form and evolve upon nucleation on elastin and provides an in vitro model that can be tuned to study hypotheses related to arterial calcification mechanisms and test drugs to stop or revert mineralization.

摘要

钙磷矿物质在大多数老年人、糖尿病患者和慢性肾病患者的富含弹性蛋白的动脉中层沉积,导致严重的心血管并发症。目前对于中层钙化还没有治愈方法,弹性蛋白层上矿物质形成的机制也不清楚。在这里,我们提出交联弹性蛋白样多肽膜作为研究中层钙化的模型。钙磷首先沉积在纤维和细丝上,然后扩散到膜中的球状结构。通过近边 X 射线光谱分析的矿物相演变与在小鼠中层钙化模型中观察到的相演变相匹配,表明这个简单的系统捕捉到了一些关键的体内发现。这项工作展示了矿物质在弹性蛋白上成核和演变的方式,并提供了一种可以调节的体外模型,用于研究与动脉钙化机制相关的假说,并测试阻止或逆转矿化的药物。

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