Impact of vascular permeability on atherosclerosis and neointima formation

血管通透性对动脉粥样硬化和新内膜形成的影响

• 批准号: 412846220
• 负责人: Professor Dr. Moritz Wildgruber
• 金额: --
• 依托单位: Klinik und Poliklinik für Radiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/412846220?language=en
• 关键词: Impact; vascular; permeability; atherosclerosis; neointima

Both de novo atherosclerosis as well as neointimal hyperplasia are characterized by inflammation of the vascular wall. While endothelial activation permits leukocytes to cross the endothelial barrier and transmigrate into the subintimal space, accumulation of cholesterol may require disruption of the endothelial integrity to enter the vessel wall. Investigating the dynamic course of endothelial dysfunction and associated subintimal inflammation has been hampered in the past as imaging of endothelial integrity in deep tissue has not been possible. Magnetic Resonance Imaging (MRI) using albumin-bound contrast agents is however able to reveal endothelial dysfunction in vivo. We propose an in vivo MR imaging approach combined with post-mortem mass spectrometry imaging to investigate endothelial dysfunction and associated subintimal inflammation during de novo atherosclerosis and neointimal hyperplasia in a hyperlipidemic rabbit model. Aim of the study is to reveal how endothelial permeability affects cholesterol influx and subintimal inflammation and to prove by in vivo imaging that restoring the endothelial barrier ameliorates the progression of atherosclerosis and the formation of neointimal hyperplasia.

新生动脉粥样硬化和新生内膜增生都以血管壁炎症为特征。虽然内皮活化允许白细胞穿过内皮屏障并迁移到内膜下空间，但胆固醇的积累可能需要破坏内皮完整性才能进入血管壁。研究内皮功能障碍和相关的内膜下炎症的动态过程在过去一直受到阻碍，因为在深层组织中内皮完整性的成像是不可能的。然而，使用白蛋白结合造影剂的磁共振成像（MRI）能够显示体内内皮功能障碍。我们提出了一种体内磁共振成像结合死后质谱成像的方法来研究高脂血症兔模型中新生动脉粥样硬化和新内膜增生期间内皮功能障碍和相关的内膜下炎症。本研究的目的是揭示内皮通透性如何影响胆固醇内流和内膜下炎症，并通过体内成像证明恢复内皮屏障可以改善动脉粥样硬化的进展和新内膜增生的形成。