Inhibition of PDGF- and TGF-beta 1-induced collagen synthesis, migration and proliferation by tranilast in vascular smooth muscle cells from spontaneously hypertensive rats

Atherosclerosis. 1995 Dec;118(2):213-21. doi: 10.1016/0021-9150(95)05607-6.

Abstract

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.

MeSH terms

  • Angioplasty, Balloon, Coronary / adverse effects
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Arterial Occlusive Diseases / prevention & control*
  • Arterial Occlusive Diseases / therapy
  • Cell Division / drug effects
  • Chemotaxis, Leukocyte / drug effects
  • Collagen / biosynthesis*
  • Drug Evaluation, Preclinical
  • Endothelium, Vascular / injuries
  • Extracellular Matrix / metabolism
  • Glycosaminoglycans / biosynthesis
  • Humans
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Platelet-Derived Growth Factor / antagonists & inhibitors*
  • Platelet-Derived Growth Factor / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / pharmacology
  • Recurrence
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / pharmacology
  • ortho-Aminobenzoates / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Glycosaminoglycans
  • Platelet-Derived Growth Factor
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • ortho-Aminobenzoates
  • Collagen
  • tranilast