Insight into the role of chondroitin sulfate E in angiogenesis

Abstract

Chondroitin sulfate E (CS‐E) is a glycosaminoglycan containing type‐E disaccharide units (sulfated at C‐4 and C‐6 of N‐acetylgalactosamine). CS‐E is covalently linked to a core protein to form chondroitin sulfate proteoglycans (PGs) that are secreted or associated with the plasma membrane of several types of cells. CS‐E‐containing PGs selectively interact with growth factors and chemokines and control various cellular and/or tissue processes. Angiogenesis is a process that is highly regulated in physiological conditions but deregulated in pathologies, leading to excess or deficient blood vessel formation. Angiogenesis regulation is orchestrated by numerous growth factors, such as vascular endothelial growth factor A, fibroblast growth factors and pleiotrophin, whose functions can be affected by CS‐containing PGs. In the present review, we focus on the emerging area of CS‐mediated angiogenesis and particularly on the critical assessment of data related to a potential role of CS‐E in controlling endothelial cell functions, focusing on angiogenesis regulation and vascular homeostasis in health and disease.

Regulation of Macrophage and Dendritic Cell Function by Chondroitin Sulfate in Innate to Antigen-Specific Adaptive Immunity

“…Regarding their sulfation patterns, CSC and CSD have anti-inflammatory activity, whereas CSA has both pro-and anti-inflammatory activities. In many cases, CSE has a potential anti-inflammatory activity, although a recent report suggests its stimulatory effect on tumor progression with the pro-inflammatory activity (6). Regarding the CS chain length, short chains such as oligosaccharides or disaccharides mostly activate inflammation, whereas the long chains serve as antiinflammatory factors.…”

“…Chondroitin sulfate (CS) is a natural biomacromolecule abundantly distributed in virtually all invertebrates and vertebrates and involved in many biological processes (19,20). Based on its structure, chain length, and sulfation patterns, CS provides specific biological functions at molecular, cellular, and organ levels, such as cell adhesion, cell division and differentiation, morphogenesis, organogenesis, and neural network formation (6,21). CS is composed of a repeating glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc) and modified with sulfate groups at varying positions on sugar residues.…”

“…Glycosaminoglycans (GAGs) are linear polysaccharides consisting of repeating disaccharide units and modified with sulfate groups at various positions on the sugar residues. The GAG chains retain negatively charged domains due to characteristics of the sulfate groups, allowing for the absorption of water and other positively charged soluble ligands, such as chemokines (1,2), cytokines (3), growth factors (4,5), and cell surface receptors (6,7). They are classified into chondroitin sulfate/dermatan sulfate (CS/DS), heparin/heparan sulfate (HP/HS), hyaluronan (HA), and keratan sulfate (KS).…”

A Biomimetic Approach toward Enhancing Angiogenesis: Recombinantly Expressed Domain V of Human Perlecan Is a Bioactive Molecule That Promotes Angiogenesis and Vascularization of Implanted Biomaterials

“…This may indicate that HS chains present in the subpopulation of rDV are sufficient to recapitulate the effects of full‐length perlecan or that CS plays a role in angiogenic growth factor binding and signaling. [ 29 ] It would be of interest to isolate populations of rDV containing only HS or CS to test the effect of each population on growth factor signaling and angiogenesis. Metabolic engineering approaches toward expression of HS‐ or CS‐rich rDV populations are also of interest in particular as cell culture conditions are known to impact on the amount and the structure of GAG chains decorating proteoglycans.…”

Glycosaminoglycan–Protein Interactions: The First Draft of the Glycosaminoglycan Interactome

“…The sulfation of CS/DS in several positions generates six disaccharide units (CS-A-E), and these different sulfation patterns, referred to as "wobble CS/DS oligosaccharide motifs," generate structural diversity at the CS-DS hybrid chain level. 8,9 The organization of HS chains in highly sulfated and iduronic acid-enriched domains (S or NS domains) interspersed with non-sulfated domains (NA or NAc domains) provides them with additional structural diversity. 1 The GAG chains, ranging from a few kDa to over a 100 kDa, contribute to the physicochemical properties and biological functions of proteoglycans.…”