Pirfenidone inhibits early myointimal proliferation but has no effect on late lesion size in rats

European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery
J R WallerM L Nicholson

Abstract

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. 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. neointimal thickness was significantly reduced in a dose-dependent manner at 14 days; pirfenidone 250 mg/kg (p<0.005), pirfenidone 500 mg/kg (p<0.001), pirfenidone 1 g/kg ( p<0.001). There were no significant differences in intimal thickening at 28 days. Expression of MMP-2, MMP-9, TIMP-1, collagen III and TGF-beta were all significantly inhibited at 14 days. Both collagen III expression and ECM deposition were reduced at 28 days ( p<0.05 and <0.002 respectively). pirfenidone reduces expression of MMPs governing smooth muscle cel...Continue Reading

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Citations

Apr 28, 2005·The Journal of Surgical Research·Nicholas R BrookMichael L Nicholson
Oct 8, 2005·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Hailan ZhouGary A Visner
Dec 31, 2009·Journal of Cardiovascular Pharmacology·Andreas BackesRuediger C Braun-Dullaeus
Jun 20, 2003·Multiple Sclerosis : Clinical and Laboratory Research·James D BowenSolomon B Margolin

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