Methods for modulating angiogenesis
AssigneeTrustees of Dartmouth College
InventorsMary Mulligan-Kehoe, Richard Powell
Life of this patent
Estimating the term…
Abstract
Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore, the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1-3 and kringles 1-4. A truncated proteolytic plasmin protein of 34 kDa is also provided.
Claims9
A method for modulating angiogenesis comprising administering an effective amount of a plasminogen activator inhibitor type 1 isoform
- lacking a reactive center loop and containing a complete heparin-binding domain, or
- lacking a reactive center loop and lacking at least a portion of a heparin-binding domain so that angiogenesis is modulated.
A method of stimulating apoptosis comprising administering an effective amount of an effective amount of a plasminogen activator inhibitor type isoform lacking a reactive center loop and lacking a heparin-binding domain so that apoptosis is stimulated.
A method of reducing cell proliferation or cell migration comprising administering an effective amount of an effective amount of a plasminogen activator inhibitor type isoform lacking a reactive center loop and lacking a heparin-binding domain so that cell proliferation or cell migration is reduced.
A method of promoting plaque regression comprising administering an effective amount of an effective amount of a plasminogen activator inhibitor type isoform lacking a reactive center loop and lacking at least a portion of the heparin-binding domain thereby promoting plaque regression.
A method of modulating angiostatin formation comprising administering an effective amount of a plasminogen activator inhibitor type isoform lacking a reactive center loop and lacking at least a portion of a heparin-binding domain so that the formation of angiostatin comprising kringles 1-3 or kringles 1-4 is modulated.
A method of treating an angiogenesis-mediated disease comprising administering an effective amount of a plasminogen activator inhibitor type isoform
- lacking a reactive center loop and containing a complete heparin-binding domain, or
- lacking a reactive center loop and lacking at least a portion of a heparin-binding domain so that the signs or symptoms associated with the angiogenesis-mediated disease are reduced.
Dependencies are inferred from the claim text.