A NEW ENDOTHELIAL CELL GROWTH FACTOR FOR WOUND HEALING

VASCULAR ENDOTHELIAL CELL GROWTH FACTOR (VEGF) IS A POTENT MITOGEN, SECRETED BY BOVINE PITUITARY FOLLICULO-STELLATE CELLS, THAT APPEARS TO BE SPECIFIC FOR VASCULAR ENDOTHELIAL CELLS. THIS SPECIFICITY SUGGESTS THAT VEGF MAY BE AN IDEAL HUMAN THERAPEUTIC AGENT FOR INDICATIONS WHERE RE-ENDOTHELIALIZATION IS DESIRED IN THE ABSENCE OF PROLIFERATION BY OTHER CELL TYPES; FOR EXAMPLE, AFTER BALLOON ANGIOPLASTY (PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY) OR IN CONJUNCTION WITH VASCULAR GRAFTING. THE LONG-RANGE GOALS OF THE PROJECT ARE TO ESTABLISH A RECOMBINANT SOURCE FOR HUMAN VEGF, AND TO USE THE RECOMBINANT PROTEIN TO DETERMINE IN ANIMAL MODELS AND (IF INDICATED) HUMAN CLINICAL TRIALS THE EFFICACY OF VEGF FOR INDICATIONS INVOLVING VASCULAR RE-ENDOTHELIALIZATION. THE PHASE I GOALS ARE TO: (1) USE N-TERMINAL PROTEIN SEQUENCE INFORMATION ALREADY OBTAINED TO ISOLATE BOVINE AND HUMAN CLONES FOR THE VEGF CODING REGION; AND (2) USE EXPRESSION OF THE CLONES, AND INACTIVATION EXPERIMENTS USINGANTIPEPTIDE ANTIBODIES, TO DEMONSTRATE THAT THE SEQUENCE OBTAINED INDEED REPRESENTS THE N-TERMINUS OF THE VEGF PROTEIN, AND TO INITIATE RECOMBINANT PRODUCTION.