| 摘要 |
<p>Although TF is expressed on perivascular cells of normal tissues and in the adventitial layer of blood vessels, these cells are sequestered from contact with circulating fVII by the tight endothelial cell layer of the normal vasculature. Therefore, differential expression of TF by endometriotic tissue makes it a specific target for inhibiting or treating endometriosis. Similarly, overexpression of PAR-2 by endometrial tissue in women with endometriosis makes it a target for inhibiting or treating endometriosis. In one embodiment, interference with binding of fVII to TF or of the TF/fVIIa to PAR-2 is accomplished by providing one or more antagonists that reduce or inhibit binding of these proteins as described above. In another embodiment, the catalytic activity of PAR-2 or the TF/fVIIa complex is inhibited by providing one or more antagonists as disclosed above. In another embodiment, TF and/or PAR-2 expression is downregulated by providing one or more inhibitory nucleic acids including, but not limited to, ribozymes, triplex-forming oligonucleotides (TFOs), antisense DNA, external guide sequences (EGSs)f siRNA, and microRNA specific for nucleic acids encoding TF or PAR-2. TF and PAR-2 antagonists can also be provided in combination with other anti-angiogenic agents or other agents used to treat endometriosis, such as those described above.</p> |
