Suppression of intimal hyperplasia by a 5-lipoxygenase inhibitor, MK-886: Studies with a photochemical model of endothelial injury

Kazunao Kondo, Kazuo Umemura, Tomohiro Ohmura, Hisakuni Hashimoto, Mitsuyoshi Nakashima

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Intimal thickening is a major complication following percutaneous transluminal coronary angioplasty, which leads to restenosis and requires reoperation. We have investigated the effect of a 5-lipoxygenase inhibitor, MK-886, a leukotriene B4 (LTB4) receptor antagonist, ONO-4057 or a LTC4 and LTD4 receptor antagonist. ONO-1078, on intimal thickening. Photochemical reaction between green light and systemically administered Rose Bengal produced intimal thickening in the rat femoral artery. Each drug was administered orally, once a day for 7 days, starting just after the endothelial injury. Both MK-886 administration, 10 mg/kg, and ONO-4057 administration, 100 mg/kg, suppressed intimal thickening level examined three weeks after endothelial injury, while similarly administered ONO-1078 did not. In cultured rat-derived smooth muscle cells, LTB4, an active metabolite of 5-lipoxygenase whose biosynthesis in air pouch exudate was suppressed by MK-886, stimulated cell migration. Based on these observations, the 5-lipoxygenase may have a key role in intimal thickening via its metabolites such as LTB4.

Original languageEnglish
Pages (from-to)635-639
Number of pages5
JournalThrombosis and Haemostasis
Volume79
Issue number3
DOIs
Publication statusPublished - 03-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

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