Dexmedetomidine suppresses the development of abdominal aortic aneurysm by downregulating the mircoRNA-21/PDCD 4 axis

Abstract

Abdominal aortic aneurysm (AAA) is a pathological state with permanent dilation, which indicates a fatal potential for aortic rupture. It has been reported that dexmedetomidine (dex) and microRNA (miR)-21 are involved in the progression of AAA. Thus, the present study aimed to investigate the joint effects of these factors on AAA treatment. For this purpose, rat models of AAA were established with enzyme perfusion and the rats were then injected with dex. Alterations in the abdom- inal aorta in rats with AAA were recorded. miR-21 expression in the rats with AAA was determined. Inflammatory factor expression was detected by western blot analysis. Subsequently, a dual-luciferase reporter gene assay was performed to verify the targeting association between miR-21 and programmed cell death protein 4 (Pdcd4). Additionally, AAA-related indices and inflammatory responses were examined by an injection of a combination of antagomiR (ant)-miR-21 and dex or lentivirus-Pdcd4-short hairpin RNA. It was found that dex markedly alleviated the development of AAA and downregulated the expression of inflammatory factors and matrix metalloproteinase in rats with AAA. The high expres- sion of miR-21, which targets Pdcd4, was observed in the rats with AAA. However, ant-miR-21 induced AAA develop- ment and inflammatory responses. Additionally, the inhibition of Pdcd4 reduced AAA development and inflammatory responses. On the whole, the present study demonstrates that dex inhibits AAA development by downregulating the miR-21/PCDP4 axis. The findings of the present study may provide novel insight for the treatment of AAA. These findings may provide a reference for the future treatment of AAA and may provide theoretical guidance for the early prevention and development of AAA.