Glycosaminoglycans (GAGs) are negatively charged polysaccharides composed of repeating disaccharide units. GAGs are normally found as proteoglycans (PGs) composed of one or more polysaccharide chains attached to a core protein (1).

PGs are present throughout all the animal kingdom, including organisms at very low levels of evolution (2). Accordingly, PGs are present in almost all the cell types where they can be found in soluble forms, in the extracellular matrix (ECM), associated to plasma membrane, or segregated into intracellular granules (1). The wide spectrum of distribution of PGs is the first prove of their biological relevance.

In the last years the studies about GAGs and PGs have increased dramatically leading to the comprehension of their biosynthesis and structure, together with the demonstration of the involvement of GAGs and PGs in various physiological processes. The biological functions of GAGs and PGs are highly diversified, ranging from relatively simple mechanical support functions to more intricate effects on various cellular processes such as cell adhesion, proliferation and differentiation. These effects are due to the ability of PGs to act as "receptors" for adhesion molecules and circulating molecules such as growth factors, cytokines, and a variety of enzymes including proteases and coagulation enzymes.

A particular class of PGs, namely the heparan sulfate PGs (HSPGs), have been demonstrated to be involved in the modulation of the neovascularization that takes place in different physiological and pathological conditions. This modulation occurs through the interaction of HSPGs with angiogenic growth factors or with negative regulators of angiogenesis, suggesting that the study of the biochemical bases of protein-HSPG interaction may help to design synthetic GAG analogs endowed with angiostatic properties.

The purpose of this review is to provide an overview of the structure/function of HSPGs, to examine the biochemical bases and physiological significance of the interaction of angiogenic growth factors with heparin and HSPGs in endothelium, and to summarize the angiostatic properties of natural and synthetic heparin-like and heparin-binding molecules.