Inhibitory effects of tranilast on expression of transforming growth factor- β isoforms and receptors in injured arteries

Tranilast (N(3,4-dimethoxycinnamoyl)anthranilic acid), an agent which in cell culture inhibits transforming growth factor- β (TGF- β) secretion and antagonises the effects of TGF- β and platelet-derived growth factor (PDGF) on cell migration and proliferation, has been reported to reduce the incidence of restenosis after angioplasty in angiographically validated human clinical trials. We investigated in a rat model of balloon angioplasty whether tranilast's effects in vivo could be attributed to inhibition of expression of TGF- β and/or its receptor types. Using a standardised reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we examined the effects of three doses of tranilast (25, 50 and 100 mg/kg) on the expression of two TGF- β isoforms, the types I and II TGF- β receptors and two putative TGF- β responses, induction of integrins α v and β 3 mRNA, 2 h after oral administration and 26 h after vessel injury. Tranilast attenuated in a dose-dependent and reversible manner the injury-induced increases in mRNA levels encoding TGF- β 1, TGF- β 3, two type I TGF- β receptors ALK-5 and ALK-2, and the type II receptor T βRII. At the highest dose mRNA levels encoding TGF- β 1 and T βRII were attenuated to levels approaching or below those observed in uninjured vessels. Messenger RNAs encoding TGF- β 3, ALK-5 and ALK-2 were all attenuated by between 70 and 74% (all P