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Adhesive interactions of platelets and their blockade with synthetic peptides
PLENARY LECTURES Thursday
June 28 1990
192 Prevention and treatment of venous thromboembolism -cc Thrombosti Research Unit, Kings College School of Medicine & Den&y, Denmark Hill, London, UK
Abstract not supplied.
193 Adhesive interactions of platelets and their blockade with synthetic peptides HA WIGER J Depament of Microbiology and Immunology Vanderbilt UniversitySchool of Medicine, Nashville, nV, USA Platelets respond to vascular injury through a series of adhesive interactions involving initial contact, spreading, and platelet thrombi formation. Each step is based on multiple bond formation between adhesive molecules and the receptors expressed on platelet membrane. Whereas adhesive molecules are present all the time in subendothelial extracellular matrix or in plasma, platelet receptors vaty in their accessibility. For example, the platelet glycoprotein IIb-IIIa complex (GPIIb-IIIa), which constitutes the receptor for fibrinogen, requires platelet activation. Such platelet activation is only partially blocked by aspirin and other non-steroidal antiinflammatory agents. GPIIb-IIIa belongs to a superfamily of integrin receptors expressed not only on platelets, but also endothelial cells and leukocytes, among others. Non-integrin receptors on platelets encompass the glycoprotein Ib complex which is a receptor forvon Willebrand factor (vWF). This receptor does not seem to require
Fibridysis (1990)4, supp. I, 77 0 LongmanGroup UK Ltd ,990
platelet activation for its binding function. Discovery of domams on adhesive molecules (fibrinogen, fibroncctin, vWF, and vitronectin), responsible for interaction with their receptors, led to the development of synthetic peptide analogues. Such analogous block adhesive interactions of platelets in ligand bindings assays in vine and in experimental models of platelet thrombi formation er vivo and in vivo. The peptides based on the sequence of the carboxyterminal segment of gamma chain of fibrinogen are highly specific for the platelet receptor for fibrinogen (GBIIb-IIIa). Peptides based on the sequence Arg-Gly-Asp (RGD), present in several adhesive proteins, interact with GPIIb-IIIa, as well as with integrin receptors on vascular endothelial cells causing their detachment in v&o. Recent studies of adhesive interactions of platelets led to a better understanding of the molecular mechanisms of thrombosis and to the development of new classes of antithrombotic agents.
June 28 1990
192 Prevention and treatment of venous thromboembolism -cc Thrombosti Research Unit, Kings College School of Medicine & Den&y, Denmark Hill, London, UK
Abstract not supplied.
193 Adhesive interactions of platelets and their blockade with synthetic peptides HA WIGER J Depament of Microbiology and Immunology Vanderbilt UniversitySchool of Medicine, Nashville, nV, USA Platelets respond to vascular injury through a series of adhesive interactions involving initial contact, spreading, and platelet thrombi formation. Each step is based on multiple bond formation between adhesive molecules and the receptors expressed on platelet membrane. Whereas adhesive molecules are present all the time in subendothelial extracellular matrix or in plasma, platelet receptors vaty in their accessibility. For example, the platelet glycoprotein IIb-IIIa complex (GPIIb-IIIa), which constitutes the receptor for fibrinogen, requires platelet activation. Such platelet activation is only partially blocked by aspirin and other non-steroidal antiinflammatory agents. GPIIb-IIIa belongs to a superfamily of integrin receptors expressed not only on platelets, but also endothelial cells and leukocytes, among others. Non-integrin receptors on platelets encompass the glycoprotein Ib complex which is a receptor forvon Willebrand factor (vWF). This receptor does not seem to require
Fibridysis (1990)4, supp. I, 77 0 LongmanGroup UK Ltd ,990
platelet activation for its binding function. Discovery of domams on adhesive molecules (fibrinogen, fibroncctin, vWF, and vitronectin), responsible for interaction with their receptors, led to the development of synthetic peptide analogues. Such analogous block adhesive interactions of platelets in ligand bindings assays in vine and in experimental models of platelet thrombi formation er vivo and in vivo. The peptides based on the sequence of the carboxyterminal segment of gamma chain of fibrinogen are highly specific for the platelet receptor for fibrinogen (GBIIb-IIIa). Peptides based on the sequence Arg-Gly-Asp (RGD), present in several adhesive proteins, interact with GPIIb-IIIa, as well as with integrin receptors on vascular endothelial cells causing their detachment in v&o. Recent studies of adhesive interactions of platelets led to a better understanding of the molecular mechanisms of thrombosis and to the development of new classes of antithrombotic agents.