Inhibition of PDGF- and TGF-beta 1-induced collagen synthesis, migration and proliferation by tranilast in vascular smooth muscle cells from spontaneously hypertensive rats.
Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) proliferate faster and are more sensitive to transforming growth factor-beta 1 (TGF-beta 1) than those of normotensive Wistar-Kyoto rats. We studied the in vitro effects of tranilast, an anti-allergic drug, on the proliferation, migration and extracellular matrix synthesis in the SHR-VSMC. There were many inhibitory effects of tranilast (30-300 microM) on SHR-VSMC. One is the effect on the proliferation stimulated with fetal bovine serum (FBS), TGF-beta 1 and platelet-derived growth factor-BB (PDGF-BB). Another is the effect on the PDGF-BB-induced migration. Lastly, tranilast exhibited inhibitory effects on spontaneous collagen synthesis and TGF-beta 1-induced collagen and glycosaminoglycan synthesis. On the other hand, collagen induced the VSMC migration concentration-dependently. These results suggest that tranilast may prevent restenosis after percutaneous transluminal coronary angioplasty.
Miyazawa
K
K
Pharmacological Laboratories, Kissei Pharmaceutical Co. Ltd., Nagano, Japan.
Kikuchi
S
S
Fukuyama
J
J
Hamano
S
S
Ujiie
A
A
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001157:Arterial Occlusive Diseases / Q000517:prevention & control* / Q000628:therapy; D002455:Cell Division / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis*; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000293:injuries; D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012008:Recurrence; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D062367:ortho-Aminobenzoates; D003094:Collagen; C012293:tranilast