Pirfenidone Inhibits Early Myointimal Proliferation but has No Effect on Late Lesion Size in Rats

• Published in: European journal of vascular and endovascular surgery 2002-03, Vol.23 (3), p.234-240
• Main Authors: Waller, J.R, Murphy, G.J, Bicknell, G.R, Sandford, R, Margolin, S.B, Nicholson, M.L
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon - adverse effects; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Carotid Arteries - drug effects; Carotid Arteries - growth & development; Carotid Artery Injuries - etiology; Disease Models, Animal; Dose-Response Relationship, Drug; Extracellular matrix; Extracellular Matrix - drug effects; Gene Expression - drug effects; Intimal hyperplasia; Male; Metalloendopeptidases - drug effects; Metalloproteinase; Pyridones - pharmacology; Rats; Time Factors; Tunica Intima - drug effects; Tunica Intima - growth & development; Tunica Intima - injuries
• ISSN: 1078-5884; 1532-2165
• DOI: 10.1053/ejvs.2001.1574

Aims: intimal hyperplasia is mediated by smooth muscle cell proliferation, migration and deposition of extracellular matrix. The anti-fibrotic agent pirfenidone has been shown to inhibit pro-fibrotic growth factors in non-vascular inflammatory models. This study investigated the effect of the novel anti-fibrotic agent pirfenidone on the development of neointima. Methods: male Sprague–Dawley rats received either standard diet or diet supplemented with pirfenidone (250, 500, 1000 mg/kg/day). Animals underwent left common carotid balloon angioplasty and were explanted at 4, 8, 14 and 28 days and analysed for intimal thickening, pro-fibrotic gene expression, extracellular matrix deposition and metalloproteinase activity. Results: neointimal thickness was significantly reduced in a dose-dependent manner at 14 days; pirfenidone 250 mg/kg (p