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Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo.

Abstract：

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

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Isaji M,Miyata H,Ajisawa Y,Takehana Y,Yoshimura N

doi

10.1038/sj.bjp.0701493

subject

Has Abstract

pub_date

1997-11-01 00:00:00

pages

1061-6

issue

6

eissn

0007-1188

issn

1476-5381

journal_volume

122

pub_type

杂志文章

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