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

• Published in: Contrast media and molecular imaging Vol. 2021; pp. 9999847 - 9
• Main Authors: Adams, Lisa C., Brangsch, Julia, Kaufmann, Jan O., Mangarova, Dilyana B., Moeckel, Jana, Kader, Avan, Buchholz, Rebecca, Karst, Uwe, Botnar, Rene M., Hamm, Bernd, Makowski, Marcus R., Keller, Sarah
• Format: Journal Article
• Language: English
• Published: England Hindawi 2021
• Subjects: Angiotensin II - genetics; Animals; Aortic Aneurysm, Abdominal - diagnostic imaging; Aortic Aneurysm, Abdominal - drug therapy; Aortic Aneurysm, Abdominal - genetics; Aortic Aneurysm, Abdominal - pathology; Apolipoproteins E - genetics; Disease Models, Animal; Doxycycline - pharmacology; Gadolinium - pharmacology; Humans; Magnetic Resonance Imaging; Mice; Organometallic Compounds - pharmacology
• ISSN: 1555-4309; 1555-4317
• DOI: 10.1155/2021/9999847

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.