Abstract
An abdominal aortic aneurysm (AAA) is a life‑threatening disease associated with a high mortality rate. At present, surgery or minimally invasive interventions are used in clinical treatment, especially for small aneurysms. However, the benefits of surgical repair are not obvious, and AAA ruptures can be prevented by aneurysm therapy to inhibit the growth of small aneurysms. Therefore, evaluating effective drugs to treat small AAAs is urgently required. Chronic inflammation is the main pathological feature of aneurysmal tissues. The aim of the present study was to investigate the protective role and underlying mechanism of ADAM metallopeptidase domain 10 (ADAM10). In the present study, a mouse model of AAA was established via porcine pancreatic elastase perfusion for 5 min per day for 14 days. ADAM10 (6 mg/kg) was injected intraperitoneally following 3 days of porcine pancreatic elastase perfusion in the ADAM10 group and the treatment continued for 10 days. The maximum inner luminal diameters of the infrarenal abdominal aortas were measured using an animal ultrasound system. The levels of high mobility group box 1 (HMGB1) and soluble receptor for advanced glycosylation end products in serum samples were measured by ELISA. Hematoxylin and eosin and elastin van Gieson staining were performed to observe morphology, integrity of the elastin layers and elastin degradation. CD68 expression was detected by immunohistochemical staining. Reverse transcription‑quantitative PCR and western blotting were used for detection of mRNA and protein levels. The gelatinolytic activities of MMP‑2 and MMP‑9 were quantified via gelatin zymography analysis. These results showed that ADAM10 inhibited HMGB1/RAGE/NF‑κB signaling and MMP activity in the pathogenesis of pancreatic elastase‑induced AAA, which provide insight into the molecular mechanism of AAA and suggested that ADAM10 may be a potential therapeutic target for AAA.