The present invention is based upon the discovery that modified
plasminogen activator inhibitor type-I (PAI-1) in which two or more amino
acid residues that do not contain a sulfhydryl group have been replaced
with amino acid residues that contain a sulfhydryl group and, therefore,
forms intramolecular disulfide bonds, have increased in vivo half-life.
Also disclosed are the modified PAI-1 proteins, derivatives and analogs
thereof, specific antibodies, nucleic acid molecules and host cells.
Methods for producing modified PAI-1, derivatives and analogs are also
provided. The invention further relates to Therapeutics, pharmaceutical
compositions and method of using the composition for treatment. The
invention may be used to inhibit angiogenesis in a subject, thereby
treating diseases or conditions associated with undesired angiogenesis
and cell proliferation. Such conditions include psoriasis, chronic
inflammation, tumor invasion and metastasis and conditions in which
angiogenesis is pathogenic. The modifide PAI-1 molecules of the present
invention are useful for the treatment, prophylaxis, management and
amelioration of cardiovascular diseases such as, but not limited to those
that are related to hyperfibrinolysis, hemophilia, and vessel leakage
syndrome.