Inpharma 1270 - 13 Jan 2001

FR-167653 may prevent restenosisafter angioplasty

FR-167653, a selective inhibitor of p38 mitogen-activated protein kinase (MAPK), may be effective in theprevention of restenosis after percutaneoustransluminal coronary angioplasty, say researchers fromJapan.

In this study, rats received oral FR-167653 3 or 10mg/kg/day or vehicle (controls), starting 3 days prior toundergoing balloon-induced injury of the left commoncarotid artery and continuing until death.

Significant inhibitionImmunohistochemical analysis revealed rapid

activation of p38 MAPK in injured arterial walls. At 48hours after vascular injury, the percentage of medialproliferating vascular smooth muscle cells wassignificantly lower in FR-167653 10 mg/kg/dayrecipients, compared with controls (19 vs 25.4%).

At 14 days after vascular injury, significant neointimalhyperplasia was observed in all injured common carotidarteries, compared with intact arteries. However, intimalthickening was inhibited in FR-167653 recipients,compared with controls; the mean intima:media ratiowas significantly lower in FR-167653 10 mg/kg/dayrecipients, compared with controls (0.697 vs 0.988).

At 8 hours after vascular injury, interleukin-1β mRNAlevels were significantly reduced in FR-167653recipients, to 18.1% of that seen in controls.

The researchers say that ‘further studies are needed toclarify the precise mechanism by which p38 MAPKpromotes neointimal hyperplasia’.Ohashi N, et al. Role of p38 mitogen-activated protein kinase in neointimalhyperplasia after vascular injury. Arteriosclerosis Thrombosis and VascularBiology 20: 2521-2526, Dec 2000 800858017

» Editorial comment: FR-167653 is in preclinical studies withFujisawa in ischaemia/reperfusion injury and septic shock.

1

Inpharma 13 Jan 2001 No. 12701173-8324/10/1270-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved