Artesunate Attenuated the Progression of Abdominal Aortic Aneurysm in a Mouse Model

Abstract

The inflammatory reaction is an important mechanism of pathogenesis of abdominal aortic aneurysm (AAA). Artesunate (AS) has been found to have anti-inflammatory effects in cardiovascular disease. The purpose of this study was to investigate whether AS could inhibit the development of AAA. AngII infused ApoE (-/-) male mice were selected as AAA model. Mice were spilt into three groups, the experimental control group (AngII), the AS treatment group (AngII+AS) and the negative control group (Vehicle) with 14 in each group. Daily administration of AS (100 mg/kg/d) or vehicle performed 3 day before the perfusion. At the end of the 28-day experiment, animal ultrasound and electronic digital caliper were used to measure the diameter of abdominal aorta. Histologic assays were performed to observe the microstructure of the aorta wall. Immunofluorescence staining was performed to detect inflammatory cells, as well as the levels of matrix metalloproteinases (MMPs). The transcription of cytokines and adhesion molecules were investigated by real-time fluorescence quantitative PCR (qPCR). Western blotting was performed to determine whether the NF-κB pathway is involved in the mechanism. While AS failed to reduce the incidence of AAA, AS effectively reduced the diameter of AAA independently of blood pressure effects. Immunofluorescence detection showed that AS effectively reduced the levels of CD45+ cells and MAC3+ macrophages as well as MMP-2 and MMP-9. qPCR revealed that AS reduced mRNA transcription levels of MMP-2, MMP-9, the cytokine IL-1β, TNF-α, adhesion molecules ICAM-1, VCAM-1. AS decreased the levels of NF-κB signaling pathway in aorta. AS can attenuate the development of AAA in mice. The possible mechanism is anti-inflammation.