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Review
. 2001 Aug;108(3):349-55.
doi: 10.1172/JCI13738.

Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena

R V Iozzo  1 , J D San Antonio
Affiliations
Review

Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena

R V Iozzo et al. J Clin Invest. 2001 Aug.
No abstract available

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Figures

Figure 1
Figure 1
Heterogeneity in structure of pericellular and cell-associated heparan sulfate proteoglycans with pro- and antiangiogenic activity. Syndecans are transmembrane proteoglycans, while glypicans are bound to the plasma membrane via a phosphoinositol linkage. Type XVIII collagen, a hybrid collagen/proteoglycan molecule, is a member of the multiplexin gene family characterized by alternating collagenous (thin lines) and noncollagenous domains (rectangles, not drawn in scale). Perlecan is a modular proteoglycan with five distinct domains. Both type XVIII collagen and perlecan are secreted products but are in close association with the cell surface and are intrinsic components of most basement membranes. Agrin, another HSPG with similarities to perlecan, is not shown. Glycosaminoglycan chains are shown as fuchsia-colored beaded strings and are not drawn to scale relative to their respective protein cores. The precise location and number of the heparan sulfate chains on type XVIII collagen are not known.
Figure 2
Figure 2
The yin (perlecan) and yang (type XVIII collagen) of angiogenic regulation by heparan sulfate proteoglycans (top panel). Perlecan, syndecans, and glypicans are proposed to act as coreceptors to deliver proangiogenic factors to their high-affinity cell surface receptors. As shown for perlecan, angiogenic stimulation might follow from its increased expression or cell surface accessibility. This would result in release of growth factors such as VEGF, carried by specific heparan sulfate sequences, or FGF2 and FGF7, bound to either heparan sulfate chains or unique regions of the protein core (middle panel). These events promote the cell proliferation phase of angiogenesis and may also trigger the synthesis and release of a battery of proteinases into the ECM milieu. Proteinases in turn would degrade perlecan, thus attenuating its growth-promoting activities, and liberate endostatin from type XVIII collagen (bottom panel). Endostatin is proposed to block VEGF- and FGF-mediated angiogenic signaling, thereby maintaining the endothelium in a quiescent state.
See this image and copyright information in PMC

References

    1. Erickson AC, Couchman JR. Still more complexity in mammalian basement membranes. J Histochem Cytochem. 2000;48:1291–1306. - PubMed
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    1. Bernfield M, et al. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 1999;68:729–777. - PubMed
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    1. Filmus, J., and Song, H.H. 2000. Glypicans. In Proteoglycans: structure, biology and molecular interactions. R.V. Iozzo, editor. Marcel Dekker Inc. New York, New York, USA. 161–176.

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