Novel angiogenic composition and use thereof

Abstract

The invention relates to a composition for promoting angiogenesis, for controlling DNA synthesis of a cell, and for controlling chemotactic motility of a cell. The invention also relates to a method for treating ischemia diseases.

1 . A composition for promoting angiogenesis, comprising a composition including a polypeptide comprising amino acid sequence or a conservative variant thereof having EGF-like domain of thrombomodulin.  
   
   
       2 . The composition of  claim 1 , wherein the polypeptide further comprises an operably linked polypeptide comprising amino acid sequence or a conservative variant of serine-threonine rich domain of thrombomodulin.  
   
   
       3 . The composition of  claim 1 , wherein the angiogenesis is to stimulate new capillary formation from endothelial cells.  
   
   
       4 . The composition of  claim 3 , wherein new capillary forms vessel.  
   
   
       5 . The composition of  claim 1 , which is used in a cell-based therapy for treating ischemia related diseases.  
   
   
       6 . The composition of  claim 3 , wherein the endothelial cells express matrix metalloproteinases or plasminogen activators.  
   
   
       7 . The composition of  claim 6 , wherein the matrix metalloproteinases or plasminogen activators mediate extracellular proteolysis leading to endothelial-cell invasion and migration during angiogenesis.  
   
   
       8 . The composition of  claim 5 , wherein the ischemia related disease is myocardial ischemia, peripheral ischemia, cerebral ischemia or deep vein thrombosis.  
   
   
       9 . The composition of  claim 1 , which helps wound healing or reconstructive surgery.  
   
   
       10 . The composition of  claim 3 , wherein the stimulation of new capillary formation is mediated through phosphorylation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase and phosphatidylinositol-3 kinase/Akt/endothelial nitric oxide synthase pathway.  
   
   
       11 . The composition of  claim 1 , comprising a gel, cream, paste, lotion, spray, suspension, solution, dispersion salve, hydrogel or ointment formulation.  
   
   
       12 . A composition for controlling DNA synthesis of a cell, comprising an agent antagonizing specifically to a fragment of polypeptide or nucleotide derived from thrombomodulin.  
   
   
       13 . The composition of  claim 12 , wherein the polypeptide further comprises an operably linked polypeptide comprising amino acid sequence or a conservative variant of serine-threonine rich domain of thrombomodulin.  
   
   
       14 . The composition of  claim 13 , wherein the DNA synthesis is a result of abnormal cell growth.  
   
   
       15 . The composition of  claim 14 , wherein the abnormal cell is a result of tumor cell proliferation.  
   
   
       16 . The composition of  claim 15 , wherein the tumor is angioma.  
   
   
       17 . A composition for controlling chemotactic motility of a cell, comprising an agent antagonizing specifically to a fragment of polypeptide or nucleotide derived from thrombomodulin.  
   
   
       18 . The composition of  claim 17 , wherein the fragment is sufficient to produce an effect of chemotactic motility on a cell.  
   
   
       19 . The composition of  claim 17 , wherein the polypeptide further comprises an operably linked polypeptide comprising amino acid sequence or a conservative variant of serine-threonine rich domain of thrombomodulin.  
   
   
       20 . The composition of  claim 12 , wherein the agent is in the form of antibody, RNAi, siRNA or antisense RNA.  
   
   
       21 . The composition of  claim 17 , which is applied to the disease or conditions selected from the group consisting of preventing tumor growth, inhibiting tumor growth, reduction in tumor volume, elimination of tumors, inhibiting metastasis, preventing metastasis, inducing dormancy of tumors and metastasis, preventing arteriosclerosis, inhibiting atherosclerosis, reducing existing plaque in blood vessels, reducing intimal plaque neovascularization, hemangioma, solid tumors, leukemia, myocardial angiogenesis, neovascular glaucoma, diabetic retinopathy, retrolental fibroplasia, arthritis, diabetic neovascularizaton, macular degeneration, wound healing, peptic ulcer, fractures, keloids, hematopoiesis, ovulation, menstruation, and placentation.  
   
   
       22 . The composition of  claim 17 , wherein the chemotactic motility is mediated through phosphorylation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase and phosphatidylinositol-3 kinase/Akt/endothelial nitric oxide synthase pathway.  
   
   
       23 . A method for treating ischemia associated with angiogenesis comprising administering to a patient in need of the treatment with a therapeutically effective amount of a polypeptide comprising amino acid sequence or a conservative variant thereof having EGF-like domain of thrombomodulin.  
   
   
       24 . The method of  claim 23 , wherein the polypeptide further comprises an operably linked polypeptide comprising amino acid sequence of serine -threonine rich domain of thrombomodulin.  
   
   
       25 . The method of  claim 23 , wherein the administration is by route of intravenous (iv), subcutaneous (sc), intraperitoneal (ip), or intramuscular (im).  
   
   
       26 . The method of  claim 23 , wherein the administration is by means of gene transfer.  
   
   
       27 . The composition of  claim 17 , wherein the agent is in the form of antibody, RNAi, siRNA or antisense RNA.