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A novel antioxidant 3,7-dihydroxy-isoflav-3-ene (DHIF) inhibits neointimal hyperplasia after vessel injury attenuating reactive oxygen species and nuclear factor-kappaB signaling.

Abstract：

:Reactive oxygen species (ROS) contribute to neointimal smooth muscle proliferation by yet to be defined mechanisms. We examined the effects of a novel isoflavone 3,7-dihydroxy-isoflav-3-ene (DHIF) on development of neointimal lesions in relation to ROS elevations and cell signaling in injured arteries. Carotid arteries of rabbits treated with vehicle or DHIF were injured with a balloon catheter and effects on proliferation, apoptosis, vessel structure, ROS, NF-kappaB activation, cyclooxygenase and gene expression examined. Seven days after injury proliferating neointimal cells were reduced by 35% (P<0.05) whilst medial cell proliferation was attenuated by 16% (P<0.05). ROS levels were elevated fourfold in injured arteries of vehicle-treated rabbits. Treatment with DHIF prevented this elevation (P<0.05). Also, NF-kappaB was activated in neointimal cells from vehicle-treated rabbits, demonstrated by nuclear accumulation of NF-kappaB-p65. DHIF not only attenuated its nuclear accumulation but also suppressed NF-kappaB-p65 expression in neointimal cells. This was accompanied by a doubling of apoptotic cell numbers (P<0.05). Expression of cyclooxygenases Cox-1 and Cox-2 were also attenuated, by 74% and 50%, respectively (P<0.05), as was MCP-1. The antiproliferative effects of DHIF persisted at 14 days, and 28 days after injury neointima growth was attenuated by 50% (P<0.05). Thus, ROS stimulates neointima growth via mechanisms involving NF-kappaB activation, cyclooxygenases and MCP-1. DHIF's ability to attenuate NF-kappaB activation suggests that it may not only be useful in preventing restenosis but also in attenuating atherosclerosis.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Kanellakis P,Pomilio G,Walker C,Husband A,Huang JL,Nestel P,Agrotis A,Bobik A

doi

10.1016/j.atherosclerosis.2008.09.005

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

66-72

issue

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(08)00624-2

journal_volume

204

pub_type

杂志文章

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A novel antioxidant 3,7-dihydroxy-isoflav-3-ene (DHIF) inhibits neointimal hyperplasia after vessel injury attenuating reactive oxygen species and nuclear factor-kappaB signaling.