Tranilast inhibits the proliferation of human coronary smooth muscle cell through the activation of p21waf1.
Restenosis after percutaneous transluminal coronary angioplasty (PTCA) occurs due to vascular smooth muscle cell proliferation and migration. Recently, tranilast, an anti-allergic drug, has been used for the prevention of restenosis after PTCA. To determine the molecular mechanism involved, the effect of tranilast on the proliferation of human coronary smooth muscle cells (SMCs) was investigated. Tranilast arrested the proliferation of human coronary SMCs at the G0/G1 phase of the cell cycle. In association with this inhibitory effect, tranilast increased p21waf1 and p53 tumor suppressor factor, and decreased cyclin-dependent kinase 2 (CDK2) activity. These results suggest that tranilast inhibits the proliferation of human coronary SMCs during restenosis after PTCA via an induction of p21waf1 and p53. Tranilast may thus allow us to prevent restenosis after PTCA by interfering with this mechanism.
Kusama
H
H
Discovery Research Laboratories, Kissei Pharmaceutical Co. Ltd., Minamiazumi, Nagano, Japan. hiroshi_kusama@pharm.kissei.co.jp
Kikuchi
S
S
Tazawa
S
S
Katsuno
K
K
Baba
Y
Y
Zhai
Y L
YL
Nikaido
T
T
Fujii
S
S
D018926:Anti-Allergic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis* / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D012333:RNA, Messenger; D062367:ortho-Aminobenzoates; D018844:Cyclin-Dependent Kinases; D015689:Oncogene Protein p21(ras); C012293:tranilast