TY - JOUR A1 - Adams, L. C. A1 - Brangsch, J. A1 - Kaufmann, Jan Ole A1 - Mangarova, D. B. A1 - Moeckel, J. A1 - Kader, A. A1 - Buchholz, R. A1 - Karst, U. A1 - Botnar, R. M. A1 - Hamm, B. A1 - Makowski, M. R. A1 - Keller, S. T1 - Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model T2 - Contrast Media & Molecular Imaging N2 - 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 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. PB - Hindawi CY - London KW - Ggadolinium KW - MRI KW - Magnetic resonance imaging KW - Osmotic minipumps KW - Tetracyclin KW - Antibiotics KW - Angiotensin II KW - LA-ICP-MS PY - 2021 UR - https://opus4.kobv.de/opus4-bam/frontdoor/index/index/docId/52701 AN - OPUS4-52701 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-527015 SP - 9999847 AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany