Molecular imaging of endothelial activation and mineralization in a mouse model of accelerated atherosclerosis

• Main Authors: Guillaume Rucher, Lucie Cameliere, Jihene Fendri, Antoine Anfray, Ahmed Abbas, Saïd Kamel, Quentin Dupas, Nicolas Delcroix, Ludovic Berger, Alain Manrique, on behalf of the STOP-AS investigators
• Format: Article
• Language: English
• Published: SpringerOpen 2019-08-01
• Series: EJNMMI Research
• Subjects: Positrons emission tomography (PET); Magnetic resonance imaging (MRI); Atherosclerosis; Mineralization; Endothelial activation
• Online Access: http://link.springer.com/article/10.1186/s13550-019-0550-5

Abstract Purpose Preclinical imaging of endothelial activation and mineralization using both positron emission tomography (PET) and magnetic resonance (MR) remains scarce. Procedures A group of uremic ApoE−/− (Ur), non-uremic ApoE−/− (NUr), and control C57Bl/6 J mice (Ctl) were investigated. Mineralization process was assessed using sodium fluoride ([18F]NaF) PET, and MR imaging combined with intravenous injection of MPIO-αVCAM-1 was used to evaluate endothelial activation. Micro- and macrocalcifications were evaluated by flame atomic absorption spectroscopy and von Kossa staining, respectively. Results Ur mice showed an active and sustained mineralization process compared to Ctl mice (p = 0.002) using [18F]NaF PET imaging. Calcium plasma level was increased in Ur (2.54 ± 0.09 mM, n = 17) compared to NUr and Ctl mice (2.24 ± 0.01, n = 22, and 2.14 ± 0.02, n = 27, respectively; p < 0.0001). Likewise, vascular calcium content was increased in Ur (0.51 ± 0.06 μg Ca2+ per milligram of dry weight aorta, n = 11) compared to NUr (0.27 ± 0.05, n = 9, p = 0.013) and Ctl (0.28 ± 0.05, n = 11, p = 0.014). Ur mice also had a higher inflammatory state using MPIO-αVCAM-1 MR (p global = 0.01, post hoc analysis Ur vs. Ctl p = 0.003) associated with increased VCAM-1 expression (p global = 0.02). Aortic remodeling at the level of the brachiocephalic trunk, brachiocephalic trunk itself, and aortic arch in Ur mice was also demonstrated using MR. Conclusions Preclinical molecular imaging allowed in vivo characterization of the early phase of atherosclerosis. [18F]NaF PET showed early and sustained vascular mineralization in uremic ApoE−/− mice. MPIO-αVCAM-1 MR imaging demonstrated aortic endothelial activation, predominantly in segments with vascular remodeling.