The Investigation Of ADAMTS-2 In Aortic Aneurysm

Background: An aortic aneurysm(AA)is a dilation compared to the normal diameter of aorta.If left untreated,the aortic wall continues to weaken then progresses to aortic dissection and rupture,which associated with a high mortality and a poor outcome.It is a multifactorial disease with complex mechanism include extracellular matrix degradation,inflammatory cell infiltration,smooth muscle cells apoptosis and phenotypic switch,oxidant stress and so on.As a member of Metalloproteinase,ADAMTS-2 is expressed in various adult tissues and play a critical role in many biological processes.However,little research has been done into the investigation of ADAMTS-2 in cardiovascular disease,especially in aortic aneurysms.In this study,we will explore the Relevance between ADAMTS-2 and aortic aneurysm.Methods: Tissue samples were collected from 10 patients with AA undergoing aortic repair,and from10 Organ donors during heart transplantation.We used HE and Masson staining for the observation of aorta structure,and examined ADAMTS-2,α-SMA,OPN,DKK3 expression in human tissues.Then we verified the expression of ADAMTS-2 in mouse AA model which induced by Ang II infusion.Finally,we clarified the relation of ADAMTS-2 and DKK-3 by immunofluorescence staining.Result: We can see that the structure of aortic wall in AA was disorganized with elastic fibers destruction,smooth muscle cells decreasing and inflammatory cell infiltration.In western blot and immunohistochemical analysis,ADAMTS-2 protein expression,both in human and mouse tissues,was significantly higher in AA group than in control group especially in tunica media.The immunofluorescence staining showed that ADAMTS-2 colocalized with DKK-3 in aortic wall.Conclusion: Our study indicated that contractile VSMCs may switch to synthetic VSMCs during the process of AA.Furthermore,ADAMTS-2 may prevent to AA evolve by this phenotypic switch with the specific substrate——DKK-3.