游离DNA在体内会使动脉壁中的磷酸钙磷灰石晶体沉淀。
Free DNA precipitates calcium phosphate apatite crystals in the arterial wall in vivo.
作者信息
Coscas Raphaël, Bensussan Marie, Jacob Marie-Paule, Louedec Liliane, Massy Ziad, Sadoine Jeremy, Daudon Michel, Chaussain Catherine, Bazin Dominique, Michel Jean-Baptiste
机构信息
UMR 1148, Inserm-Paris7, Denis Diderot University, Xavier Bichat Hospital, 75018 Paris, France; UMR 1173, Inserm-Paris11, Faculty of Health Sciences Simone Veil, Versailles Saint-Quentin-en-Yvelines University, Paris-Saclay University, 78180 Montigny-le-Bretonneux, France; Department of Vascular Surgery, Ambroise Paré University Hospital, AP-HP, 92104 Boulogne-Billancourt, France; UMR 1018, Inserm-Paris11, CESP, Versailles Saint-Quentin-en-Yvelines University, Paris-Saclay University, Paul Brousse Hospital, 94807 Villejuif, France.
UMR 1148, Inserm-Paris7, Denis Diderot University, Xavier Bichat Hospital, 75018 Paris, France; Jules Verne University of Picardie and Department of Vascular Surgery, Amiens-Picardie University Hospital, 80054 Amiens, France.
出版信息
Atherosclerosis. 2017 Apr;259:60-67. doi: 10.1016/j.atherosclerosis.2017.03.005. Epub 2017 Mar 4.
BACKGROUND AND AIMS
The arterial wall calcium score and circulating free DNA levels are now used in clinical practice as biomarkers of cardiovascular risk. Calcium phosphate apatite retention in the arterial wall necessitates precipitation on an anionic platform. Here, we explore the role of tissue-free DNA as such a platform.
METHODS
The first step consisted of histological observation of samples from human and rat calcified arteries. Various stains were used to evaluate colocalization of free DNA with calcified tissue (alizarin red, fluorescent Hoechst, DNA immunostaining and TUNEL assay). Sections were treated by EDTA to reveal calcification background. Secondly, a rat model of vascular calcifications induced by intra-aortic infusions of free DNA and elastase + free DNA was developed. Rat aortas underwent a micro-CT for calcium score calculation at 3 weeks. Rat and human calcifications were qualitatively characterized using μFourier Transform Infrared Spectroscopy (μFTIR) and Field Emission-Scanning Electron Microscopy (FE-SEM).
RESULTS
Our histological study shows colocalization of calcified arterial plaques with free DNA. In the intra-aortic infusion model, free DNA was able to penetrate into the arterial wall and induce calcifications whereas no microscopic calcification was seen in control aortas. The calcification score in the elastase + free DNA group was significantly higher than in the control groups. Qualitative evaluation with μFTIR and FE-SEM demonstrated typical calcium phosphate retention in human and rat arterial specimens.
CONCLUSIONS
This translational study demonstrates that free DNA could be involved in arterial calcification formation by precipitating calcium phosphate apatite crystals in the vessel wall.
背景与目的
动脉壁钙评分和循环游离DNA水平目前在临床实践中用作心血管风险的生物标志物。动脉壁中磷酸钙磷灰石的潴留需要在阴离子平台上沉淀。在此，我们探讨游离DNA作为这样一个平台的作用。
方法
第一步是对人和大鼠钙化动脉的样本进行组织学观察。使用各种染色方法评估游离DNA与钙化组织的共定位（茜素红、荧光Hoechst、DNA免疫染色和TUNEL检测）。切片用EDTA处理以显示钙化背景。其次，建立了通过主动脉内输注游离DNA以及弹性蛋白酶+游离DNA诱导血管钙化的大鼠模型。在3周时对大鼠主动脉进行微型计算机断层扫描（micro-CT）以计算钙评分。使用μ傅里叶变换红外光谱（μFTIR）和场发射扫描电子显微镜（FE-SEM）对大鼠和人类的钙化进行定性表征。
结果
我们的组织学研究显示钙化动脉斑块与游离DNA共定位。在主动脉内输注模型中，游离DNA能够穿透动脉壁并诱导钙化，而在对照主动脉中未观察到微观钙化。弹性蛋白酶+游离DNA组的钙化评分显著高于对照组。用μFTIR和FE-SEM进行的定性评估表明，在人和大鼠动脉标本中存在典型的磷酸钙潴留。
结论
这项转化研究表明，游离DNA可能通过在血管壁中沉淀磷酸钙磷灰石晶体而参与动脉钙化的形成。
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