Heparin and related glycosaminoglycans exhibit anticoagulant, antithrombotic and hemorrhagic activities, as well as a number of other diverse effects. Among the latter are the effects of heparin on lipoprotein lipase and lipoproteins, smooth muscle cell proliferation, fibronectin and angiogenesis. Heparan sulfate proteoglycans are ubiquitous cell-surface constituents and are also integral components of the glomerular basement membrane. Defects in metabolism and/or structure of heparin-related glycosaminoglycans may result in thromboses, hemorrhagic states, disorders in kidney function or lipid disposition. The underlying objective of the conference is to bring together researchers studying the various aspects of heparin-related glycosaminoglycans with the aim to develop new directions for investigation and application. This request is suggested for consideration by NIHLB, NIGMS and NIDDK. Heparin itself comprises a mixture of macromolecules with a range in molecular weights and differences in fine-structure. Thus heparin can be separated into anticoagulantly active and inactive components. Additionally, separations according to molecular weight provide fractions with different degrees of activity. The anticoagulant activity of heparin is ascribed to its effect in accelerating the action of antithrombin against thrombin, factor Xa and various other procoagulant proteins. Anticoagulantly active heparin has thus been shown to contain a unique oligosaccharide sequence that is critical for the binding to antithrombin. Such a sequence has also been found to be present in the cell-surface heparan sulfates that exhibit antithrombin- accelerating activity. The relation between structure and function for other effects of the proteoglycans is presently not known. The specific influences of structure, charge and degree of sulfation will be discussed fully at this conference. Other effects of heparin such as its action on platelets, smooth-muscle cells and atherosclerosis will also be subjects to be taken up at the meeting. Various other activities of heparin, such as its promotion of lipoprotein lipase and its interactions with fibronectin, histine-rich glycoprotein,, and growth factors will be discussed, and results of clinical studies of heparins as related to venous thrombosis, pulmonary embolism, incomplete stroke and arterial disease will be discussed in detail.
