Tranilast inhibits the proliferation of human coronary smooth muscle cell through the activation of p21(waf1)

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) occu rs due to vascular smooth muscle cell proliferation and migration. Recently , tranilast, an anti-allergic drug, has been used for the prevention of res tenosis after PTCA. To determine the molecular mechanism involved, the effe ct of tranilast on the proliferation of human coronary smooth muscle cells (SMCs) was investigated. Tranilast arrested the proliferation of human coro nary SMCs at the G0/G1 phase of the cell cycle. In association with this in hibitory effect, tranilast increased p21(waf1) and p53 tumor suppressor fac tor, and decreased cyclin-dependent kinase 2 (CDK2) activity. These results suggest that tranilast inhibits the proliferation of human coronary SMCs d uring restenosis after PTCA via an induction of p21(waf1) and p53. Tranilas t may thus allow us to prevent restenosis after PTCA by interfering with th is mechanism. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.