TRANILAST INHIBITS THE PROLIFERATION, CHEMOTAXIS AND TUBE FORMATION OF HUMAN MICROVASCULAR ENDOTHELIAL-CELLS IN-VITRO AND ANGIOGENESIS IN-VIVO

1 First developed as an antiallergic drug, tranilast inhibits chemical mediator release from mast cells. In the present study, we examine th e effects of tranilast on angiogenesis in vitro and in vivo and discus s the application of tranilast for angiogenic diseases. 2 Tranilast in hibited significantly the proliferation (IC50: 136 mu M, 95% confidenc e limits: 134-137 mu M) and vascular endothelium growth factor (VEGF)- induced chemotaxis (IC50: 135 mu M, 95% confidence limits: 124-147 mu M) of human dermal microvascular endothelial cells (HDMECs) at concent rations greater than 25 mu g ml(-1). No toxicity to HDMECs measuring b y LDH release and no inhibitory effects on metalloproteinase (MMP)-2 a nd MMP-9 activity were observed even at 100 mu g ml(-1) (306 mu M). 3 Tube formation of HDMECs cultured on the matrigel as an in vitro angio genesis model was inhibited by tranilast in a concentration-dependent manner. The IC50 value and 95% confidence limits were 175 mu M and 151 -204 mu M, respectively. 4 In vivo angiogenesis was induced in mice by the subcutaneous injection of matrigel containing 30 ng ml(-1) VEGF a nd 64 mu g ml(-1) heparin. Tranilast was administered orally twice a d ay for 3 days. Tranilast dose-dependently suppressed angiogenesis in t he matrigel and a significant change was observed at a dose of 300 mg kg(-1). 5 These results indicate that tranilast is an angiogenesis inh ibitor which may be beneficial for the improvement of angiogenic disea ses such as proliferative diabetic retinopathy, age-related macular de generation, tumour invasion and rheumatoid arthritis.