Linked Life Data

19162037

Source:http://linkedlifedata.com/resource/pubmed/id/19162037

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-4-6
pubmed:abstractText
Preventive treatment with cannabinoid agonists has been reported to reduce the infarct size in a mouse model of myocardial ischemia/reperfusion. Here we investigated the possible cardioprotective effect of selective CB(2) cannabinoid receptor activation during ischemia. We performed left coronary artery ligature in C57Bl/6 mice for 30 min, followed by 24 h of reperfusion. Five minutes before reperfusion, mice received intraperitoneal injection of the CB(2) selective agonist JWH-133 (20 mg/kg) or vehicle. Infarct size was assessed histologically and by cardiac troponin I (cTnI) ELISA. Immunohistochemical analysis of leukocyte infiltration, oxidative stress in situ quantification, real-time RT-PCR analysis of inflammatory mediators as well as western blots for kinase phosphorylation was also performed. In addition, we studied chemotaxis and integrin expression of human neutrophils in vitro. JWH-133 significantly reduced the infarct size (I/area at risk: 19.27%+/-1.91) as compared to vehicle-treated mice (31.77%+/-2.7). This was associated with a reduction of oxidative stress and neutrophil infiltration in the infarcted myocardium, whereas activation of ERK 1/2 and STAT-3 was increased. Preinjection of PI3K inhibitor LY294002, MEK 1/2 inhibitor U0126 and JAK-2 inhibitor AG-490 partially abrogated the JWH-133 mediated infarct size reduction. No changes in cardiac CXCL1, CXCL2, CCL3, TNF-alpha, and ICAM-1 expression levels were found. Furthermore, JWH-133 inhibited the TNF-alpha induced chemotaxis and integrin CD18/CD11b (Mac-1) upregulation on human neutrophils. Our data suggest that JWH-133 administration during ischemia reduces the infarct size in a mouse model of myocardial ischemia/reperfusion through a direct cardioprotective activity on cardiomyocytes and neutrophils.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1095-8584
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
612-20
pubmed:meshHeading
pubmed-meshheading:19162037-Animals, pubmed-meshheading:19162037-Antigens, CD11b, pubmed-meshheading:19162037-Cannabinoids, pubmed-meshheading:19162037-Cell Movement, pubmed-meshheading:19162037-Chemotactic Factors, pubmed-meshheading:19162037-Disease Models, Animal, pubmed-meshheading:19162037-Humans, pubmed-meshheading:19162037-Intercellular Adhesion Molecule-1, pubmed-meshheading:19162037-Intracellular Space, pubmed-meshheading:19162037-Mice, pubmed-meshheading:19162037-Myocardial Infarction, pubmed-meshheading:19162037-Myocardial Reperfusion Injury, pubmed-meshheading:19162037-Myocardium, pubmed-meshheading:19162037-Neutrophils, pubmed-meshheading:19162037-Oxidative Stress, pubmed-meshheading:19162037-Reactive Oxygen Species, pubmed-meshheading:19162037-Receptor, Cannabinoid, CB2, pubmed-meshheading:19162037-Signal Transduction, pubmed-meshheading:19162037-Tumor Necrosis Factor-alpha
pubmed:year
2009
pubmed:articleTitle
CB(2) cannabinoid receptor activation is cardioprotective in a mouse model of ischemia/reperfusion.
pubmed:affiliation
Division of Cardiology, Foundation for Medical Researches, Department of Internal Medicine, University Hospital, Geneva, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't