Versican Degradation and Vascular Disease

Abstract

Versican is an abundant proteoglycan in the blood vessel wall that is increased after vascular injury and accumulates in advanced atherosclerotic plaques. Versican is a large molecule with domains that mediate binding to cytokines, enzymes, lipoproteins, other extracellular matrix molecules, and signaling receptors. There is evidence that versican exists in the normal, as well as the diseased, vessel wall as discrete fragments, which represent these functional domains. We review the literature on versican degradation in vascular tissue and the function of versican domains, all of which suggest that proteolytic modification of versican may have physiologic as well as pathologic implications for the vascular system.

Extracellular matrix in the trabecular meshwork

“…2) is a large lectican, which can bind to hyaluronan chains and interact with various other ECM proteins or cellular receptors and has four alternative mRNA splicing variants. (Wight 2002;Wu et al 2005;Kenagy et al 2006) TM cells express these different splice forms and the ratios are changed with mechanical stretch, TGFβ, TNFα and IL-1α treatments (Keller, et. al.…”

“…Versican is also cleaved by specific proteinases at various sites, which results in fragments with very different activities such as stimulation of cell division, disruption of chemokine function and apoptosis. (Kenagy et al 2006) In the TM, the versican fragment produced by ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) 1 or 4, which cleave between Glu441 and Ala442 in the alpha GAG domain, is found in moderate abundance and may be higher in areas of high segmental outflow (Bradley, et. al., manuscript in preparation).…”

Synthesis and Organization of Hyaluronan and Versican by Embryonic Stem Cells Undergoing Embryoid Body Differentiation

“…Isoforms V0 and V1 usually appear as two high-molecular-mass products that migrate in the 350-to 450-kDa range on SDS-PAGE (Sandy et al 2001;Kenagy et al 2006;Seidelmann et al 2008). For ESCs or EBs after 4 days of differentiation, little, if any, immunoreactivity appeared in the gels above the 250 molecular weight marker where V0 and V1 usually run ( Figure 4A).…”

Adamts5 Deletion Blocks Murine Dermal Repair through CD44-mediated Aggrecan Accumulation and Modulation of Transforming Growth Factor β1 (TGFβ1) Signaling

“…For example, evidence of a role for ADAMTS activity in dermal repair comes from the finding that human skin contains abundant aggrecanase-generated catabolic fragments of versican V0 and V1 (5) and that both aggrecan and versican are associated with the dermal region of the hair follicle (7). Moreover, to place dermal matrix turnover in a broader context, cleavage of the hyalectans aggrecan, versican, and brevican by one or more aggrecanases (ADAMTS1, -4, -5, -8, -9, and -15) occurs in the remodeling of cartilage (10), aorta (11,12), spinal cord (13), meniscus (14,15) intervertebral disc (16), adipose tissue (17), and brain (18). HA 2 in the skin is most abundant in the epidermal layer (6), and it undergoes partial fragmentation in both the dermis and epidermis of human skin explants (19).…”