Inventory of Coagulation Inhibitors from Animals Feeding on Blood

Markwardt, Fritz

doi:10.1055/s-0038-1648892

Cited by 17 publications

(13 citation statements)

References 39 publications

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“…The extreme diversity of horsefly anti-thrombosis components also reveals the anti-thrombosis molecular mechanisms of the traditional Eastern medicine insect material. Antihemostatic compounds of blood-sucking arthropods have been distinguished into several groups such as inhibitors of coagulation factors (Factors VII, V, thrombin, and Xa) and platelet functions, fibrin(ogen)olytic enzymes, and vasoactive peptides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). No fibrin(ogen)olytic enzyme from insects was characterized although a tick fibrin(ogen)olytic metalloprotease has been reported previously (11).…”

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confidence: 99%

Anti-thrombosis Repertoire of Blood-feeding Horsefly Salivary Glands

Wang

Yang

et al. 2009

Molecular & Cellular Proteomics

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Blood-feeding arthropods rely heavily on the pharmacological properties of their saliva to get a blood meal and suppress immune reactions of hosts. Little information is available on antihemostatic substances in horsefly salivary glands although their saliva has been thought to contain wide range of physiologically active molecules. In traditional Eastern medicine, horseflies are used as antithrombosis material for hundreds of years. By proteomics coupling transcriptome analysis with pharmacological testing, several families of proteins or peptides, which exert mainly on anti-thrombosis functions, were identified and characterized from 60,000 pairs of salivary glands of the horsefly Tabanus yao Macquart (Diptera, Tabanidae). They are: (I) ten fibrin(ogen)olytic enzymes, which hydrolyze specially alpha chain of fibrin(ogen) and are the first family of fibrin(ogen)olytic enzymes purified and characterized from arthropods; (II) another fibrin(ogen)olytic enzyme, which hydrolyzes both alpha and beta chain of fibrin(ogen); (III) ten Arg-Gly-Asp-motif containing proteins acting as platelet aggregation inhibitors; (IV) five thrombin inhibitor peptides; (V) three vasodilator peptides; (VI) one apyrase acting as platelet aggregation inhibitor; (VII) one peroxidase with both platelet aggregation inhibitory and vasodilator activities. The first three families are belonging to antigen five proteins, which show obvious similarity with insect allergens. They are the first members of the antigen 5 family found in salivary glands of blood sucking arthropods to have anti-thromobosis function. The current results imply a possible evolution from allergens of blood-sucking insects to anti-thrombosis agents. The extreme diversity of horsefly anti-thrombosis components also reveals the anti-

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confidence: 99%

Anti-thrombosis Repertoire of Blood-feeding Horsefly Salivary Glands

Wang

Yang

et al. 2009

Molecular & Cellular Proteomics

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“…[9,10]. Apart from the discovery of tabanin, a potent inhibitor of thrombin [4,7,8] in one of the largest species (Tabanus bovinus) which shows similarities to the mode of action of hirudin, horsefly anticoagulants have not been studied. Our results confirmed the existing knowledge on horsefly anticoagulants in routine coagulation assays (TT, PT, APTT).…”

Section: Discussionmentioning

confidence: 99%

“…Antihaemostatic compounds of bloodsucking arthropods have been distinguished into several groups such as inhibitors of fac-tors VII and V, thrombin (antithrombins), the prothrombinase complex (mainly inhibitors of factor Xa), platelet functions and fibrinolytic enzymes [1,3,4]. Most haematophagous arthropods have been found to produce several different anticoagulants each inhibiting different factors of the coagulation pathways.…”

Section: Introductionmentioning

confidence: 99%

“…A thrombin inhibitor, isolated from Tabanus bovinus, was named tabanin [8]. Tabanin is thought to be an approximately 7-kD peptide [4]; however, its amino acid sequence is unknown. In addition to tabanin, a platelet aggregation inhibitor and a potent glycoprotein IIb/IIIa fibrinogen receptor antagonist have been isolated from deerflies, Chrysops sp.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Anticoagulant Activities in Salivary Gland Extracts of Four Horsefly Species (Diptera, Tabanidae)

Kazimírová

Šulanová²,

Kozánek³

et al. 2001

Pathophysiol Haemos Thromb

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Anticoagulant activities against the extrinsic and intrinsic coagulation pathways were identified in salivary gland extracts (SGE) prepared from four tabanids (Hybomitra muehlfeldi, Tabanus autumnalis, Haematopota pluvialis, Heptatoma pellucens). All extracts prolonged human plasma clotting time in a dose-dependent manner and inhibited thrombin activity in the chromogenic substrate assay. Horsefly SGE did not inhibit factor Xa. Partial purification of SGE proteins using reversed-phase high-performance liquid chromatography revealed species-specific differences in the elution profiles and range of fractions with anticoagulant activities.

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“…After the characterization of the first specific thrombin inhibitor hirudin by Fritz Markwardt, many other thrombin inhibitors have been detected in different haematophagus animals [1]. Today hirudin is produced by recombinant technology Hirudin and other thrombin inhibitors have been studied in a number of clinical trials and at present several oral thrombin inhibitors are being developed by different pharmaceutical companies.…”

Section: Introductionmentioning

confidence: 99%

Current Developments in Antithrombotic Therapy: The Role of Antithrombin Agents

Hk¹

2002

Pathophysiol Haemos Thromb

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Hirudin, the specific thrombin inhibitor from medicinal leeches, is now produced by recombinant technology. r-Hirudin and to a lesser extent polyethyleneglycol-coupled hirudin (PEG-hirudin) have been used in many clinical trials. Hirudin has been shown to be more effective than low molecular weight heparin in the prevention of deep venous thrombosis after total hip replacement. In (acute) coronary syndromes hirudin as well as a synthetic hirudin analogue bivalirudin have been studied in large clinical trials. Higher doses of hirudin were associated with an increased risk of bleeding. A large-scale study with bivalirudin in patients with acute MI (the HERO-2 trial) has not shown a reduction in mortality but a 30% reduction of reinfarction within 96 h. Hirudin and argatroban have been successfully used in patients with heparin-induced thrombocytopenia type II. Several orally active thrombin inhibitors are being developed. The combined use of subcutaneous and oral administration of melagatran in patients with hip or knee replacement has led to promising results. It is likely that in the future thrombin inhibitors will replace other forms of anticoagulation in a number of indications.

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Inventory of Coagulation Inhibitors from Animals Feeding on Blood

Cited by 17 publications

References 39 publications

Anti-thrombosis Repertoire of Blood-feeding Horsefly Salivary Glands

Anti-thrombosis Repertoire of Blood-feeding Horsefly Salivary Glands

Identification of Anticoagulant Activities in Salivary Gland Extracts of Four Horsefly Species (Diptera, Tabanidae)

Current Developments in Antithrombotic Therapy: The Role of Antithrombin Agents

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