Linked Life Data

21070851

Source:http://linkedlifedata.com/resource/pubmed/id/21070851

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-3
pubmed:abstractText
Previous studies have suggested that increased levels of endocannabinoids in various cardiovascular disorders (e.g., various forms of shock, cardiomyopathies, atherosclerosis) through the activation of CB(1) cannabinoid receptors may promote cardiovascular dysfunction and tissue injury. We have investigated the role of the main endocannabinoid anandamide-metabolizing enzyme (fatty acid amide hydrolase; FAAH) in myocardial injury induced by an important chemotherapeutic drug, doxorubicin (DOX; known for its cardiotoxicity mediated by increased reactive oxygen and nitrogen species generation), using well-established acute and chronic cardiomyopathy models in mice. The DOX-induced myocardial oxidative/nitrative stress (increased 4-hydroxynonenal, protein carbonyl, and nitrotyrosine levels and decreased glutathione content) correlated with multiple cell death markers, which were enhanced in FAAH knockout mice exhibiting significantly increased DOX-induced mortality and cardiac dysfunction compared to their wild type. The effects of DOX in FAAH knockouts were attenuated by CB(1) receptor antagonists. Furthermore, anandamide induced enhanced cell death in human cardiomyocytes pretreated with FAAH inhibitor and enhanced sensitivity to ROS generation in inflammatory cells of FAAH knockouts. These results suggest that in pathological conditions associated with acute oxidative/nitrative stress FAAH plays a key role in controlling the tissue injury that is, at least in part, mediated by the activation of CB(1) receptors by endocannabinoids.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1873-4596
pubmed:author
pubmed:copyrightInfo
Published by Elsevier Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
179-95
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Fatty acid amide hydrolase is a key regulator of endocannabinoid-induced myocardial tissue injury.
pubmed:affiliation
Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't