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.

Differentially expressed genes and canonical pathways in the ascending thoracic aortic aneurysm – The Tampere Vascular Study

“…The samples were collected from patients undergoing cardiac surgery in the Heart Center of Tampere University Hospital with informed consent 9 . Patient information was collected with questionnaires and from the patient database of the hospital.…”

“…In addition, changes occur in regard to collagen, especially the type IV collagen related to the vasa vasorum 4 . Multiple gene expression changes of important inflammatory and ECM-remodeling machinery genes have been demonstrated between healthy and diseased ascending aorta, for example in the expression of ECM remodeling matrix metalloproteases 2 and 9 (MMP-2 and −9) 7 , 8 and a disintegrin and metalloproteinases (ADAMs) 8 and 15 9 . Also, the expression of tissue inhibitors (TIMPs) of these metalloproteases has recently come in to the focus of research in aortic diseases, especially in ATAA research 5 .…”

Aiming at One-Stage Corrective Surgery for Extended Thoracic Aortic Dilatation

“…Inflammatory and endothelial cells, medial degeneration, and intima thickness were estimated as previously described and expressed as PSU. 13 Histological analysis included the evaluation of cystic medial degeneration (CMD) and intimal thickness. CMD was estimated on a scale from 0 to 3 (0, normal media; 1, mild degeneration; 2, moderate degeneration; and 3, severe degeneration).…”

Immunoglobulin G4–positive ascending thoracic aortitis may be prone to dissection

“…Inflammatory cells, intensity of inflammation, medial degeneration, intima cellularity, and thickness were estimated as previously described and expressed as point score units (PSU). 9 For semiquantitative analyses, inflammation was graded as none, mild, moderate, or severe (0, 1, 2, or 3, respectively). Medial degeneration was graded as patchy, moderate, or severe again on a scale of 0 to 3.…”

“…6,7 Recent attempts to elucidate the association of inflammation with AAD and AD have generated theories on activation of aortic wall inflammation together with aortic wall remodeling. 8,9 The fundamental question to the clinician is to identify new tools to help in decisionmaking concerning resection for AAD.…”