Evaluation of Enzymes Involved in Proteoglycan Degradation in the Wall of Abdominal Aortic Aneurysms

Abstract

The abdominal aortic aneurysm (AAA) wall represents an extreme example of arterial remodeling with disturbed elastin, collagen and proteoglycan metabolism. The aim of this study was to evaluate enzymes involved in the degradation of glycosaminoglycan chains and core proteins of proteoglycans in the AAA wall. The study material consisted of wall samples from 10 AAA. Fragments of 5 normal abdominal aortas from organ donors were used as a control. The activity of endoglycosidases, exoglycosidases and sulfatases was measured using colorimetric methods. To assess matrix metalloproteinases (MMPs), Western blot and zymography were performed. The activity of endoglycosidase degrading chondroitin-4-sulfate was lower in the AAA wall. Endoglycosidase degrading heparan sulfate and dermatan sulfate, arylosulfatase B, as well as all the exoglycosidases assessed demonstrated higher activities in the AAA wall. Furthermore, increased expression of MMP1, MMP2 and MMP9 was also shown in the AAA wall. Zymography revealed decreased activity of pro-MMP2 and presence of pro-MMP9 in the AAA wall compared to the wall of normal aorta. Extensive changes in the activity of glycosaminoglycan-degrading enzymes and MMPs may influence the organization of the extracellular matrix network and lead to previously demonstrated changes in the proteoglycan and glycosaminoglycan content in the AAA wall.

Ace inhibitors potently reduce vascular inflammation, results of an open proof-of-concept study in the abdominal aortic aneurysm

“…This conclusion follows the conclusion of Wilmink et al, [15] but is remarkable as the anti-inflammatory potency of ACE-inhibition through ramipril exceeds that of any of the other interventions reported to date, and as its activity also includes suppression of MMP9 and cathepsin S expression, proteases that are thought to be critically involved in the process of aortic wall debilitation [23,[33][34][35][36][37].…”

“…This shift may (partly) account for the reduced expression of the proteases MMP9, cathepsin L and S which are all considered instrumental in the process AAA growth. [33][34][35][36][37] An effect of ramipril on cellular activation was not restricted to macrophages as indicated by a broad reduction in the expression of markers of cytotoxic T-cell and B-cell activation, cell types that are also involved in the process of AAA formation and progression [9,10]. The Anti-Inflammatory Potential of ACE-Inhibitors A critical question is whether and how these clear effects translate into clinical effect such as growth and rupture in the context of AAA, and cardiovascular events in the context of atherosclerosis.…”

Alterations in Aortic Cellular Constituents during Thoracic Aortic Aneurysm Development

“…Although the change in total medial collagen was shown to be minimal, the reduction in gap area may be driven by a loss in both the cellular content (discussed below) as well as proteoglycan matrix. This is supported by Kowalewski et al, 30 demonstrating elevated activity of proteoglycan degrading enzymes in abdominal aortic aneurysm specimens. This may suggest that significant proteoglycan degradation contributes to the medial atrophy observed during TAA formation.…”

Interaction of Biomechanics with Extracellular Matrix Components in Abdominal Aortic Aneurysm Wall

“…These findings reflect that proteoglycans and collagens are in close association with each other and proteoglycans stabilize the structure of collagen fibers. 33,36 Consequently, these facts emphasize the important role of compensatory collagens and proteoglycans synthesis in maintaining the structural integrity and stability of the aortic wall during AAA progression, as a reaction to increased mechanical loads.…”