Abstract
Angiogenesis, the sprouting of new blood vessels from existing vasculature, involves multiple complex biological processes, and it is an essential step for hemostasis, tissue healing and regeneration. Angiogenesis stimulants can ameliorate human disease conditions including limb ischemia, chronic wounds, heart disease, and stroke. The current strategies to improve the bioavailability of pro-angiogenic growth factors, including VEGF and FGF2, have remained largely unsuccessful. This study demonstrates that small molecules, termed click-xylosides, can promote angiogenesis in the in vitro matrigel tube formation assay and the ex ovo chick chorioallantoic membrane assay, depending on their aglycone moieties. Xyloside treatment enhances network connectivity and cell survivability, thereby, maintaining the network structures on matrigel culture for an extended period of time. These effects were achieved via the secreted xyloside-primed glycosaminoglycans (GAG) chains that in part, act through an ERK1/2 mediated signaling pathway. Through the remodeling of GAGs in the extracellular matrix of endothelial cells, the glycan approach, involving xylosides, offers great potential to effectively promote therapeutic angiogenesis.
Highlights
Angiogenesis, the formation of new blood vessels from existing ones, is an essential biological process during development for organogenesis and wound repair
Since GAG chains are essential in mediating interactions between growth factors and receptors, the excess secreted GAGs primed by click-xylosides are expected to promote angiogenesis
human umbilical vein endothelial cells (HUVECs) were seeded on matrigel in media containing 100 μM of the tested xylosides, and tube formation was examined after 8 hours
Summary
Angiogenesis, the formation of new blood vessels from existing ones, is an essential biological process during development for organogenesis and wound repair. Blood vessels are generally latent and angiogenesis is stimulated only in particular conditions such as open wounds, hypoxia and the cycling ovary during pregnancy [1]. This multi-step process is highly regulated via the spatial and temporal distribution of stimulators and inhibitors [1]. Insufficient angiogenesis impedes healing and regeneration but it affects the survival of existing cells and tissues.
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