Method of inhibiting platelet aggregation and clot formation

摘要

The instant invention provides methods and compositions for the treatment, prevention and diagnosis of for example, platelet aggregation or clot formation in a subject. The invention inhibits the activity of decreases the amount of neutrophils in the subject by inhibiting the activity or production of IL-6, interferon-gamma, STAT1, or cathepsin G. The invention addresses decreasing the amount of neutrophils in an attempt to treat subjects that have or are at risk of developing a vascular occlusive disease, an ischemia or reperfusion injury, an acute or chronic inflammatory state, autoimmune disease, myelodysplastic syndrome, tissue injury from surgery or accidental trauma, acute bacterial or viral infection, has undergone a microvascular surgical reconstructive procedure, is receiving granulocyte colony stimulating factor therapy, receiving stem cell therapy, or has sickle cell anemia.

主权项

1. A method of inhibiting platelet aggregation or clot formation in a subject, comprising:
identifying a subject that has previously shown resistance or failure to respond to aspirin treatment for inhibiting platelet aggregation or clot formation; and administering to the subject an amount of a cathepsin G inhibitor selected from the group consisting of Z-gly-leu-phe-chloromethyl ketone, Gly-Leu-Phe, benzyloxycarbonyl-Gly-Leu-Phe-chloromethyl ketone, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 15, monocyte neutrophil elastase inhibitor, maspin, secretory leukocyte protease inhibitor, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, β-ketophosphonate 1 (JNJ-10311795; RWF-355871), Ac-Ala-Ala-ANva-OPh, Ac-Ala-Ala-ANle-OPh, Ac-Ala-Ala-ANle-OCH2CF3 and Ac-Ala-Ala-ANle-OE effective to inhibit platelet aggregation or clot formation in the subject; thereby inhibiting platelet aggregation or clot formation in the subject.