Résumé
The anticlotting and antithrombotic activities of heparin, heparan sulfate, low molecular weight heparins, heparin and heparin-like compounds from various sources used in clinical practice or under development are briefly reviewed. Heparin isolated from shrimp mimics the pharmacological activities of low molecular weight heparins. A heparan sulfate from Artemia franciscana and a dermatan sulfate from tuna fish show a potent heparin cofactor II activity. A heparan sulfate derived from bovine pancreas has a potent antithrombotic activity in an arterial and venous thrombosis model with a negligible activity upon the serine proteases of the coagulation cascade. It is suggested that the antithrombotic activity of heparin and other antithrombotic agents is due at least in part to their action on endothelial cells stimulating the synthesis of an antithrombotic heparan sulfate.
Sujets)
Humains , Animaux , Bovins , Anticoagulants/pharmacologie , Endothélium vasculaire/cytologie , Fibrinolytiques/pharmacologie , Héparine/pharmacologie , Héparitine sulfate/pharmacologie , Anticoagulants/composition chimique , Anticoagulants/métabolisme , Crustacea , Fibrinolytiques/composition chimique , Fibrinolytiques/métabolisme , Glycosaminoglycanes/métabolisme , Glycosaminoglycanes/pharmacologie , Héparine bas poids moléculaire/composition chimique , Héparine bas poids moléculaire/métabolisme , Héparine bas poids moléculaire/pharmacologie , Héparine/métabolisme , Héparitine sulfate/biosynthèse , ThonRésumé
The distribution and structure of heparan sulfate and heparin are briefly reviewed. Heparan sulfate is a ubiquitous compound of animal cells whose structure has been maintained throughout evolution, showing an enormous variability regarding the relative amounts of its disaccharide units. Heparin, on the other hand, is present only in a few tissues and species of the animal kingdom and in the form of granules inside organelles in the cytoplasm of special cells. Thus, the distribution as well as the main structural features of the molecule, including its main disaccharide unit, have been maintained through evolution. These and other studies led to the proposal that heparan sulfate may be involved in the cell-cell recognition phenomena and control of cell growth, whereas heparin may be involved in defense mechanisms against bacteria and other foreign materials. All indications obtained thus far suggest that these molecules perform the same functions in vertebrates and invertebrates