Impact of vascular permeability on atherosclerosis and neointima formation

• Applicant: Professor Dr. Moritz Wildgruber
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 412846220

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.

• DFG Programme: Research Grants