Development of new heparin-like compounds and other antithrombotic drugs and their interaction with vascular endothelial cells

• Published in: Brazilian journal of medical and biological research 2001-06, Vol.34 (6), p.699-709
• Main Authors: Nader, H B, Pinhal, M A, Baú, E C, Castro, R A, Medeiros, G F, Chavante, S F, Leite, E L, Trindade, E S, Shinjo, S K, Rocha, H A, Tersariol, I L, Mendes, A, Dietrich, C P
• Format: Article
• Language: English
• Subjects: Animals; Anticoagulants - chemistry; Anticoagulants - metabolism; Anticoagulants - pharmacology; antithrombotic agents; antithrombotic agents, development for clinical use; BIOLOGY; Cattle; Crustacea; crustacean heparin-like compounds, antithrombotic activity; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Fibrinolytic Agents - chemistry; Fibrinolytic Agents - metabolism; Fibrinolytic Agents - pharmacology; Glycosaminoglycans - metabolism; Glycosaminoglycans - pharmacology; heparan sulfate, antithrombotic activity; Heparin - chemistry; Heparin - metabolism; Heparin - pharmacology; heparin, anticlotting activity; Heparin, Low-Molecular-Weight - chemistry; Heparin, Low-Molecular-Weight - metabolism; Heparin, Low-Molecular-Weight - pharmacology; Heparitin Sulfate - biosynthesis; Heparitin Sulfate - pharmacology; Humans; low molecular weight heparins, preparation and antithrombotic activity; MEDICINE, RESEARCH & EXPERIMENTAL; Structure-Activity Relationship; Tuna; vascular endothelial cells
• ISSN: 0100-879X; 1414-431X; 0100-879X; 1414-431X
• DOI: 10.1590/S0100-879X2001000600002

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.