Prominent inhibitory effects of tranilast on migration and proliferation of and collagen synthesis by vascular smooth muscle cells.
To obtain some ideas about prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we examined the effects of transilast (anti-allergic agent) on migration and proliferation of, and collagen synthesis by, cultured vascular smooth muscle cells (VSMC) from the thoracic aorta of WKY rats. Tranilast was added to culture medium containing 10% fetal calf serum (FCS). The cultures were pulse-labeled with 3H-thymidine (TdR) or 3H-proline (Pro). TdR and Pro uptake into VSMC were measured. The effect of tranilast on migration of VSMC was examined by using culture dishes of an original design. We also examined the inhibitory effects of various drugs, such as a Ca antagonist, an angiotensin converting enzyme (ACE) inhibitor, a phosphodiesterase inhibitor, elastase, colchicine, and mitomycin C, on proliferation and migration of VSMC. Our data showed that the inhibitory effects of tranilast on migration and proliferation of, and collagen synthesis by, VSMC were prominent. Maximal percentage inhibition of proliferation, migration and collagen synthesis was 60.8 +/- 2.3%, 52.7 +/- 14.7% and 62.1 +/- 8.1%, respectively. On the other hand, the inhibitory effects of other drugs, with the exception of colchicine and mitomycin C, on proliferation and/or migration of VSMC were not very strong. Although the inhibitory effects of colchicine and mitomycin C were strong in vitro, their clinical usefulness may be limited by systemic side-effects. These results indicate the potential usefulness of tranilast for prevention of restenosis of coronary arteries after PTCA.
Tanaka
K
K
4th Department of Internal Medicine, Shimane Medical University, Japan.
Honda
M
M
Kuramochi
T
T
Morioka
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D016685:Mitomycin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D062367:ortho-Aminobenzoates; C035100:nilvadipine; C059498:olprinone; D016685:Mitomycin; D003094:Collagen; D010196:Pancreatic Elastase; C012293:tranilast; D009543:Nifedipine; D003078:Colchicine