Source:http://linkedlifedata.com/resource/pubmed/id/11888511
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2002-3-12
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pubmed:abstractText |
Freshly solubilized A beta peptides synergistically increase the magnitude of the constriction induced by endothelin-1 (ET-1), via the activation of a pro-inflammatory pathway. We report that mevinolin and mevastatin, two inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase are able to completely abolish the vasoactive properties of A beta in rat aortae. Mevinolin also appears to oppose the increased vascular reactivity to ET-1 induced by interleukin 1-beta and phospholipase A(2) suggesting that statins display some anti-inflammatory properties. We show that freshly solubilized A beta stimulates prostaglandin E(2) and F(2 alpha) production (by 6 and 3.6 times, respectively) in isolated rat aortae and that mevinolin completely antagonizes this effect confirming the anti-inflammatory action of mevinolin ex vivo in rat aortae. In addition, we observed that A beta vasoactivity is not mediated nor modulated by mevalonic acid suggesting that the anti-inflammatory action of the statins are not related to an inhibition of HMG-CoA reductase activity. Differentiated human neuroblastoma cells (IMR32) were used to assess the neurotoxic effect of pre-aggregated A beta by quantifying the release of lactate dehydrogenase (LDH) in the cell culture medium. A beta appears to enhance LDH release by 30% in IMR32 cells, an effect that can be completely opposed by mevastatin. Taken together these data show that statins can antagonize the effect of A beta in different assays and provide new clues to understand the prophylactic action of the statins against Alzheimer's disease.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alprostadil,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Anticholesteremic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Lovastatin,
http://linkedlifedata.com/resource/pubmed/chemical/compactin
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9150
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
161
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
293-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11888511-Alprostadil,
pubmed-meshheading:11888511-Alzheimer Disease,
pubmed-meshheading:11888511-Amyloid beta-Peptides,
pubmed-meshheading:11888511-Analysis of Variance,
pubmed-meshheading:11888511-Animals,
pubmed-meshheading:11888511-Anticholesteremic Agents,
pubmed-meshheading:11888511-Aorta,
pubmed-meshheading:11888511-Cells, Cultured,
pubmed-meshheading:11888511-Dinoprostone,
pubmed-meshheading:11888511-Dose-Response Relationship, Drug,
pubmed-meshheading:11888511-Lovastatin,
pubmed-meshheading:11888511-Male,
pubmed-meshheading:11888511-Models, Animal,
pubmed-meshheading:11888511-Rats,
pubmed-meshheading:11888511-Rats, Sprague-Dawley,
pubmed-meshheading:11888511-Reference Values,
pubmed-meshheading:11888511-Vasculitis,
pubmed-meshheading:11888511-Vasoconstriction
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pubmed:year |
2002
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pubmed:articleTitle |
Statins inhibit A beta-neurotoxicity in vitro and A beta-induced vasoconstriction and inflammation in rat aortae.
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pubmed:affiliation |
Department of Psychiatry, The Roskamp Institute, University of South Florida, 3515 E. Fletcher Avenue, Tampa, FL 33613, USA. dparis@hsc.usf.edu
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, Non-P.H.S.
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