Author/Authors :
Adams, Lisa C Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany , Brangsch, Julia Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany , Kaufmann, Jan O Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany , Mangarova, Dilyana B Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany , Moeckel, Jana Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany , Kader, Avan Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany , Buchholz, Rebecca Westfalische Wilhelms-Universitat Munster - Munster, Germany , Karst, Uwe Westfalische Wilhelms-Universitat Munster - Munster, Germany , Botnar, Rene M School of Biomedical Engineering and Imaging Sciences - St Thomas’ Hospital Westminster Bridge Road - London, UK , Hamm, Bernd Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany , Makowski, Marcus R Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany , Keller, Sarah Department of Radiology - Charite-Universitaetsmedizin Berlin - Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin - Chariteplatz - Berlin, Germany
Abstract :
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.
Keywords :
Aortic , Abdominal , Doxycycline , ECM
