A disintegrin and metalloprotease -8 and -15 and susceptibility for ascending aortic dissection

Abstract

Background. Dilatation of the ascending aorta (AA) is affected by extra-cellular matrix modifications and inflammation. A disintegrin and metalloproteases (ADAMs) may reveal differences between AA and ascending aortic dissection (AD). We characterized the inflammatory histology of AD and AA and examined the role of ADAM8 and -15 in these diseases. Material and methods. Aortic wall histology and immunohistochemistry for leukocytes, T- and B-lymphocytes, plasma cells, macrophages, endothelial cells, smooth muscle cells, cell proliferation, elastase and Van-Gieson-staining were performed to 40 consecutive patients that underwent surgery for AA or AD. The expressions of ADAM8 and -15 mRNA and proteins were evaluated using QRT-PCR and immunohistochemistry. Results. Thirty-four patients were enrolled, of which 29 had AA and five had AD of the ascending aorta. B-cells throughout the aortic wall and intimal plasma cells were more numerous during AD as compared with AA (p < 0.05). The gene expressions for ADAM8 and -15 were notably lower in AA as compared with AD. The median for down-regulation of ADAM8 and -15 in AA was –2.7 and −1.8, respectively. ADAM8 and -15 were mainly found in the media layer in patients with AD. Two of the patients with AA and increased ADAMs developed AD of the remaining aorta. Conclusions. The involvement of ADAM8 and -15 together with inflammation consisting of B-cells may indicate active remodelling of the aortic wall leading to AD.

Key Words::

• Adam8 protein
• Adam15 protein
• thoracic aorta
• dilatation
• dissection

Acknowledgements

The authors wish to thank Ms Ulla Jukarainen and Eini Eskola for their skilful technical assistance. This study was supported by research funding from The Competitive Research Foundation of Tampere University Hospital (Grant 9L058), Tuberculosis Foundation, The Finnish Heart Association, The Finnish Cultural Foundation, European Union 7th Framework Program, grant number 201668, Atheroremo, and Orion Pharmos Research Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.