Development of new heparin-like compounds and other antithrombotic drugs and their interaction with vascular endothelial cells.
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.
Nader
H B
HB
Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua 3 de Maio 100, 04044-020 São Paulo, SP, Brazil. hbnader.bioq@epm.br
Pinhal
M A
MA
Baú
E C
EC
Castro
R A
RA
Medeiros
G F
GF
Chavante
S F
SF
Leite
E L
EL
Trindade
E S
ES
Shinjo
S K
SK
Rocha
H A
HA
Tersariol
I L
IL
Mendes
A
A
Dietrich
C P
CP
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D003445:Crustacea; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D013329:Structure-Activity Relationship; D014413:Tuna
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D006493:Heparin; D006495:Heparin, Low-Molecular-Weight; D006497:Heparan Sulfate