Summary
Heparin and related polysaccharides have long been used for therapautic intervention
in different disease states related to thromboembolic complications. The localization
and functional availability of heparin-like components in the body is mostly confined
to cell surfaces and extracellular matrix/basement membranes. Their strategic position
particularly in the vascular system enables heparinoids linked to various core proteins
(designated as heparan sulfate proteoglycans) to interact with a variety of heparin-binding
proteins such as apolipoproteins, lipases, proteases and protease inhibitors, matrix
proteins as well as surface receptors on other cells and microorganisms. The variety
in gene expression of respective core proteins and differences in glycosaminoglycan
side chains are relevant factors for the selectivity of these interactions. Heparinoid-associated
core proteins serve as co-receptors for a number of metabolic properties of vascular
cells as well as for the regulation of cellular processes, particular as they relate
to cell growth and differentiation in angiogenesis. Moreover, heparan sulfate proteoglycans
contribute to the process of lipoprotein retention in the vessel wall and the onset
of atherosclerosis. Elucidation of molecular properties, functions and their role
in vascular diseases can lead to valuable information for the design of heparinoid
analogues to be used for pharmacological intervention.
Keywords
Heparin - heparan sulfate - proteoglycans - co-receptors - endothelial cells - matrix
proteins - antithrombin - lipoprotein lipase - atherosclerosis - angiogenesis