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.

• Authors: Mari Levula, Timo Paavonen, Timo Valo, Markku Pelto-Huikko, Reijo Laaksonen, Mika Kahonen, Ari Huovila, Terho Lehtimaki, Matti Tarkka, Ari A Mennander
• Journal: Scandinavian journal of clinical and laboratory investigation (Scand J Clin Lab Invest) Vol. 71 Issue 6 Pg. 515-22 (Oct 2011) ISSN: 1502-7686 [Electronic] England
• PMID: 21728902 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• ADAM Proteins
• ADAM15 protein, human
• ADAM8 protein, human

Topics

• ADAM Proteins (genetics, metabolism)
• Aged
• Aortic Dissection (enzymology, pathology, surgery)
• Aorta (enzymology, pathology, surgery)
• Aortic Aneurysm (enzymology, pathology, surgery)
• B-Lymphocytes (pathology)
• Down-Regulation
• Female
• Humans
• Male
• Membrane Proteins (genetics, metabolism)
• Middle Aged
• Real-Time Polymerase Chain Reaction
• Transcription, Genetic