Impact of vascular permeability on atherosclerosis and neointima formation

原发性动脉粥样硬化和新生内膜增生的特征都是血管壁的炎症。虽然内皮激活允许白细胞穿过内皮屏障并迁移到内膜下空间，但胆固醇蓄积可能需要破坏内皮完整性才能进入血管壁。过去，由于无法对深部组织中的内皮完整性进行成像，因此研究内皮功能障碍和相关内膜下炎症的动态过程一直受到阻碍。然而，使用白蛋白结合造影剂的磁共振成像（MRI）能够揭示体内内皮功能障碍。我们提出了一种结合死后质谱成像的体内MR成像方法，以研究高血压兔模型中新生动脉粥样硬化和新生内膜增生过程中的内皮功能障碍和相关内膜下炎症。本研究旨在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改善动脉粥样硬化的进展和新生内膜增生的形成。

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.