Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-4-17
pubmed:abstractText
Probucol [4,4'-[(1-methylethylidene)bis(thio)]bis-[2,6-bis(1,1-dimethylethyl)phenol]] was withdrawn from the United States market because it failed to inhibit atherosclerosis in human femoral arteries, yet the drug was shown subsequently to inhibit atherosclerosis in human carotid arteries, and probucol monosuccinate ester is presently being tested in a phase III clinical trial as an antiatherosclerotic compound based on its anti-inflammatory properties. Inflammatory macrophages are implicated in arterial remodeling associated with atherosclerosis, and probucol inhibits experimental atherosclerosis in part by decreasing macrophages in lesions. However, the impact of probucol on remodeling is unknown, although such knowledge could help explain why the drug's benefit on human atherosclerosis is controversial. We therefore examined the effect of probucol on remodeling of the common carotid artery in apolipoprotein E-deficient mice. We observed that during de novo atherosclerosis, plaque growth was fully compensated by expansive remodeling, such that lumen area was unaffected. Early lesions were composed almost entirely of macrophages, and their contribution to lesion area progressively decreased thereafter. Probucol significantly decreased plaque area, expression of vascular cell adhesion molecule-1, and proliferation of intimal cells, resulting in delayed macrophage accumulation in the vessel. Probucol also decreased the production and activity of matrix metalloproteinases-2 and -9, independent of the plasmin protease system, and this was associated with an inhibition of expansive remodeling, resulting in lumen loss. These studies show that probucol attenuates compensatory remodeling associated with de novo atherosclerosis, probably via its anti-inflammatory properties. Our findings suggest that lumen volume is not a suitable surrogate to assess the antiatherosclerotic activity of probucol and related drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
321
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
477-84
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Probucol [4,4'-[(1-methylethylidene)bis(thio)]bis-[2,6-bis(1,1-dimethylethyl)phenol]] inhibits compensatory remodeling and promotes lumen loss associated with atherosclerosis in apolipoprotein E-deficient mice.
pubmed:affiliation
Centre for Vascular Research and Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, and Royal North Shore Hospital, Sydney, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't