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Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model

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Lisa C. Adams, Julia Brangsch, Jan O. Kaufmann, Dilyana B. Mangarova, Jana Moeckel, Avan Kader, Rebecca Buchholz, Uwe Karst, Rene M. Botnar, Bernd Hamm, Marcus R. Makowski, Sarah Keller

Original languageEnglish
Article number9999847
JournalContrast Media and Molecular Imaging
Volume2021
DOIs
Published2021

Bibliographical note

Publisher Copyright: © 2021 Lisa C. Adams et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Background. Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE-/- model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods. Nine ApoE-/- mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE-/- animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results. In a previous study, we found that approximately 25% of angiotensin II-infused ApoE-/- mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE-/- mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE-/- mice showed significantly lower contrast-to-noise (CNR) values (p=0.017) in MRI compared to ApoE-/- mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion. The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.

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