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

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.

Injectable Shear‐Thinning Hydrogels with Sclerosing and Matrix Metalloproteinase Modulatory Properties for the Treatment of Vascular Malformations

“…[ 34 ] Unfortunately, its effects on endothelial remodeling in vitro did not translate to in vivo through systemic administration. [ 35 ] On the other hand, local use could mimic the in vitro observations of previous reports. [ 36 ] Here, we showed that STB gels loaded with DOX have ablative properties ( Figure ) as well as MMP inhibitory effects (Figure 4) and showed endothelial modulation (Figure 6).…”

An evidence update to explore molecular targets and protective mechanisms of apigenin against abdominal aortic aneurysms based on network pharmacology and experimental validation

“…Without timely treatment, the mortality of ruptured AAA is extremely high [9]. However, unexpectable complications after surgery, high in-hospital mortality of ruptured AAA, and controversial clinical strategies for small unruptured AAA all remind us that it's urgent to explore associated mechanisms of AAA progression and screen effective strategies for AAA treatment [10][11][12]. Phytochemicals, also known as secondary plant metabolites [13], are bioactive plant-derived chemical constituents [14].…”