Versican undergoes specific alterations in the fine molecular structure and organization in human aneurysmal abdominal aortas

Abstract

Versican is the major matrix proteoglycan in aortic wall and participates in various biological functions of the tissue. In the present study the molecular characteristics of versican isolated from normal human aorta as well as those of versican expressed in aneurysmal aortic tissue were examined. Versican was isolated by combined anion-exchange and gel permeation chromatography and was further characterized by high-performance liquid chromatography, polyacrylamide gel electrophoresis and immunoblotting. In both tissues versican is exclusively substituted with chondroitin sulfate chains, in contrast to other human tissues where both chondroitin and dermatan sulfate chains are attached onto versican core proteins. Except for the significant decrease in the concentration of versican in the aneurysmal tissue, this PG undergoes specific alterations in the aneurysmal tissue. The molecular size of versican isolated from diseased tissue is decreased with a simultaneous increase in the ratio of glycosaminoglycan to protein in this tissue. The latter reflect the extensive fragmentation of versican in the diseased tissue and most probably the generation of shorter peptides enriched to glycosaminoglycan chains. Although the size of chondroitin sulfate chains is identical in both versican preparations, a significant increase in the percentage of 6-sulfated disaccharides is observed in chondroitin sulfate chains of versican in aneurysmal aortas, which is accompanied by decrease in 4-sulfated and non-sulfated units.

Tissue diffusion and retention of metalloproteinases in ascending aortic aneurysms and dissections

“…Indeed, according to previous investigations, this metalloprotease is much more efficient in degrading PGs than other MMPs, such as MMP-1 and MMP-9. Therefore, matrilysin and stromelysin-1 probably share the ability to bind to the sulfated residues of the mucoid substance and to degrade the core of the native PGs of the aortic wall, thereby profoundly modifying the glycosaminoglycan environment of the aortic SMCs [37]. Similar data have already been reported in osteoarthritis, where matrilysin was associated with modified glycosaminoglycans of pathological cartilage [38], and in atherosclerosis in association with versican [34].…”

“…They can also activate other proteases and cleave PGs [35]. Versican is one of the PGs that can be degraded by MMP-7 [36,37]. Indeed, according to previous investigations, this metalloprotease is much more efficient in degrading PGs than other MMPs, such as MMP-1 and MMP-9.…”

“…Concerning elastic fiber fragmentation, another important feature of these diseases, MMP-7 may cause elastolysis not only by a direct effect but also via serpinase activity [37], a complex pathway through which some MMPs inactivate inhibitors of serine proteases. MMP-7 also breaks down fibronectin, a glycoprotein whose integrity is important for the maintenance of cell adhesion to the ECM [39].…”

A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) expression increases in acute aortic dissection

“…The concentration of versican in the arterial wall was 89% lower in patients with aneurysms (Theocharis et al, 2001). Further research found a significant increase in the versican degradation fragment in the vascular wall in aortic aneurysm tissues (Theocharis et al, 2003). These studies suggest that versican degradation may be associated with the progression of aortic dissection or aneurysm.…”

Versican Degradation and Vascular Disease

“…For example, in addition to the full-length core protein (at >350 kDa), we observed strongly reactive bands migrating at 160 and 300 kDa in Western blots of deglycosylated extracts of normal human aorta (Sandy et al 2001). Such lower molecular weight species were also observed in conditioned medium of cultured human smooth muscle cells (SMCs) (Sandy et al 2001) and in human atherosclerotic plaques (Formato et al 2003) and aneurysms (Theocharis et al 2003). Moreover, distinct fragments of versican were detected in normal bovine and mouse aortas (Figure 2).…”