Abstract: A method of modulating vascularization in a tissue of a mammal comprises controlling a PAR signaling pathway (e.g., the PAR-1 or PAR-2 signaling pathway) in a mammalian tissue, for example, by controlling phosphorylation of tissue factor cytoplasmic domain (i.e., phosphorylation of Ser258 of the cytoplasmic tail of TF). In a preferred method pathological is treated by administering to a mammal suffering from pathological neovascularization, a therapeutically effective amount of a PAR signaling pathway inhibitor. Preferably the mammal is a human.

Abstract: The present invention provides compositions and methods of treating neovascular diseases, such as a retinal neovascular diseases and tumors, by administering to a patient suffering from a neovascular disease or tumor a vascular development inhibiting amount of a combination of the angiogenesis suppressing drugs comprising an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one compound selected from the group consisting of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor. Compositions for use in the methods include an admixture of an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor, together with a pharmaceutically acceptable excipient.

Abstract: An isolated peptide useful as a selective antagonist of mammalian R-cadherin comprises 3 to 30 amino acid residues, three contiguous residues of the peptide having the amino acid sequence Ile-Xaa-Ser; wherein Xaa is an amino acid residue selected from the group consisting of Asp, Asn, Glu, and Gln. Preferably Xaa is Asp or Asn. In one preferred embodiment the peptide is a cyclic peptide having 3 to 10 amino acid residues arranged in a ring. The selective R-cadherin antagonist peptides of the invention are useful for inhibiting the targeting of stem cells, such as endothelial precursor cells, to developing vasculature, for inhibiting R-cadherin mediated cellular adhesion, and for inhibiting retinal angiogenesis.