Daphnetin suppresses experimental abdominal aortic aneurysms in mice via inhibition of aortic mural inflammation

Rupture of abdominal aortic aneurysm (AAA) is a devastating event that can be prevented by inhibiting the growth of small aneurysms. Therapeutic strategies targeting certain events that promote the development of AAA must be developed, in order to alter the course of AAA. Chronic inflammation of the aortic mural is a major characteristic of AAA and is related to AAA formation, development and rupture. Daphnetin (DAP) is a coumarin derivative with anti-inflammatory properties that is extracted from Daphne odora var. However, the effect of DAP on AAA development remains unclear. The present study investigated the effect of DAP on the formation and development of experimental AAAs and its potential underlying mechanisms. A mice AAA model was established by intra-aortic infusion of porcine pancreatic elastase (PPE), and mice were intraperitoneally injected with DAP immediately after PPE infusion. The maximum diameter of the abdominal aorta was measured by ultrasound system, and aortic mural changes were investigated by Elastica van Gieson (EVG) staining and immunohistochemical staining. The results demonstrated that DAP significantly suppressed PPE-induced AAA formation and attenuated the depletion of aortic medial elastin and smooth muscle cells in the media of the aorta. Furthermore, the density of mural macrophages, T cells and B cells were significantly attenuated in DAP-treated AAA mice. In addition, treatment with DAP resulted in a significant reduction in mural neovessels. These findings indicated that DAP may limit the formation and progression of experimental aneurysms by inhibiting mural inflammation and angiogenesis. These data confirmed the translational potential of DAP inclinical AAA inhibition strategies.