Effects of Pemirolast and Tranilast on Intimal Thickening After Arterial Injury in the Rat

Abstract

We previously reported that tranilast, an antiallergic agent, reduced intimal thickening after endothelial injury in rats. In this study, to verify whether or not antiallergic agents inhibit intimal thickening, we investigated the effect of pemirolast on intimal thickening after endothelial injury and compared its effect with that of tranilast. Administration of two antiallergic agents, pemirolast (0.1, 1, and 10 mg/kg, p.o.) and tranilast (300 mg/kg, p.o., daily), was begun 2 days before endothelial injury and continued until the animals were killed. Endothelial injury in the rat femoral artery was induced by a photochemical reaction between localized irradiation by green light and intravenously administered rose bengal. To evaluate intimal hyperplasia, we measured the cross-sectional area of the intima 21 days after endothelial damage. Pemirolast at doses of 0.1, 1, and 10 mg/kg reduced the intimal area to 2.10 +/- 0.33, 1.36 +/- 0.19, and 1.35 +/- 0.18 (x0.01 mm2), respectively, and tranilast showed a tendency to reduce the intimal area, which was 1.86 +/- 0.35 x 0.01 mm2, compared with findings for controls (2.83 +/- 0.49 x 0.01 mm2). In rat A10 vascular smooth-muscle cells, we investigated the effects of antiallergic agents on migration by using a modified Boyden chamber assay and on proliferation by using the bromodeoxyuridine-incorporation assay. Two antiallergic agents inhibited in a concentration-dependent manner both migration and proliferation of smooth muscle cells stimulated by platelet-derived growth factor. These results suggest that antiallergic agents directly inhibit migration of smooth-muscle cells to the intima from the media and proliferation in the intima, and that pemirolast has more potent antihyperplastic action than does tranilast. Antiallergic agents may be effective in preventing restenosis after coronary angioplasty.

Approaches for prevention of restenosis

“…Tranilast was found to significantly suppress vascular intimal hyperplasia in rabbit artery after balloon injury 65,66 and in pig coronary arteries after balloon angioplasty and stent implantation. 67 …”

Targeting Fibrosis for the Treatment of Heart Failure: A Role for Transforming Growth Factor‐β

“…More promising, is a range of agents with demonstrated TGF‐β inhibitory actions for which a mechanism of action is less clear. These agents include compounds such as tranilast and pirfenidone that inhibit the actions of TGF‐β as well as other pathogenic growth factors [115,116].…”

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model

“…This antiproliferative action has been investigated in several animal models of arterial injury for the prevention of vascular intimal thickening. [32][33][34][35][36] p21 Waf1/Cip1 has been reported to play an important regulatory role in the control of cell proliferation. It is an intrinsic inhibitor of cyclin/cyclin-dependent kinase complexes [12][13][14][15] and can limit cell progression through G 1 to S phase.…”