RESUMO
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.
Assuntos
Humanos , Animais , Bovinos , Anticoagulantes/farmacologia , Endotélio Vascular/citologia , Fibrinolíticos/farmacologia , Heparina/farmacologia , Heparitina Sulfato/farmacologia , Anticoagulantes/química , Anticoagulantes/metabolismo , Crustáceos , Fibrinolíticos/química , Fibrinolíticos/metabolismo , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/farmacologia , Heparina de Baixo Peso Molecular/química , Heparina de Baixo Peso Molecular/metabolismo , Heparina de Baixo Peso Molecular/farmacologia , Heparina/metabolismo , Heparitina Sulfato/biossíntese , AtumRESUMO
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.
Assuntos
Anticoagulantes/farmacologia , Endotélio Vascular/efeitos dos fármacos , Fibrinolíticos/farmacologia , Heparina/farmacologia , Heparitina Sulfato/farmacologia , Animais , Anticoagulantes/química , Anticoagulantes/metabolismo , Bovinos , Crustáceos , Endotélio Vascular/citologia , Fibrinolíticos/química , Fibrinolíticos/metabolismo , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/farmacologia , Heparina/química , Heparina/metabolismo , Heparina de Baixo Peso Molecular/química , Heparina de Baixo Peso Molecular/metabolismo , Heparina de Baixo Peso Molecular/farmacologia , Heparitina Sulfato/biossíntese , Humanos , Relação Estrutura-Atividade , AtumRESUMO
Sulfated glycosaminoglycans were isolated from 23 species of 13 phyla of invertebrates and characterized by their electrophoretic migration in three different buffer systems coupled with enzymatic degradation using bacterial heparinase, heparitinases and chondroitinase AC. Heparan sulfate is a ubiquitous compound present in all species analyzed whereas chondroitin sulfate was present in 20 species and heparin-like compounds in 12 species of the invertebrates. The heparin-like compounds were purified from the echinoderm Mellita quinquisperforata (sand dollar) and the crustacean Ucides cordatus (crab) with anticoagulant activities of 60 and 52 IU/mg, respectively. Degradation of these heparins with heparinase produced significant amounts of the trisulfated disaccharide typical of mammalian heparins. This was confirmed by 13C-NMR spectroscopy of the crab heparin. An updated phylogenetic tree of the distribution of sulfated glycosaminoglycans in the animal kingdom is also presented.
Assuntos
Glicosaminoglicanos/análise , Invertebrados/química , Animais , Anticoagulantes/análise , Condroitina Liases , Sulfatos de Condroitina/análise , Crustáceos/química , Equinodermos/química , Eletroforese em Gel de Ágar , Glicosaminoglicanos/química , Glicosaminoglicanos/isolamento & purificação , Heparina/análise , Heparina Liase , Heparitina Sulfato/análise , Espectroscopia de Ressonância Magnética , Polissacarídeo-Liases , Sulfatos/análiseRESUMO
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.
Assuntos
Fenômenos Fisiológicos Celulares , Heparina , Heparitina Sulfato , Animais , Glicosaminoglicanos , Heparina/fisiologia , Heparitina Sulfato/biossíntese , Heparitina Sulfato/fisiologia , Invertebrados , Moluscos , VertebradosRESUMO
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