Linked Life Data

20951693

Source:http://linkedlifedata.com/resource/pubmed/id/20951693

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-6
pubmed:abstractText
Inactivation of phosphatase and tensin homologue deleted on chromosome ten (PTEN) decreases cardiac contractility under basal conditions and induces cardioprotection against ischemia-reperfusion injury. However, the pharmacological effect of PTEN inhibitors on cardiac contractility has not been studied before. In the present study, we investigated the hypothesis that PTEN inhibition decreases cardiac contractility in mice. We first exposed isolated mouse hearts to the PTEN inhibitor bpV(phen) (40?M), the phosphoinositide-3 kinase inhibitor wortmannin (1?M), and the PTEN-resistant PIP3 analog 3-phosphorothioate-PtdIns(3,4,5)P3 (3-PT-PTP, 0.5?M) for 10min. Left ventricular pressure was measured by a Mikro-tip pressure catheter. We then inhibited PTEN in mice by intra-peritoneal injection of VO-OHpic (10?g/kg) 30min before ischemia and then exposed them to 30min of ischemia and 120min of reperfusion. At the end of the experiments, hearts were isolated for measurement of myocardial infarct size by 1.5% triphenyltetrazolium chloride. Left ventricular systolic pressure and heart rate were significantly decreased by bpV(phen). Consistent with the result, the maximal rate of left ventricular pressure increase or decrease was significantly decreased by bpV(phen). 3-PT-PIP3 mimicked the effect of bpV(phen), and the opposite effect on cardiac contractility was seen with wortmannin. Moreover, inhibition of PTEN in vivo by VO-OHpic decreased left ventricular systolic pressure and heart rate before ischemia, but resulted in an increase in cardiac functional recovery and a decrease in myocardial infarct size after ischemia-reperfusion. In conclusion, PTEN inhibition causes a negative inotropic and chronotropic effect while inducing cardioprotection against ischemia-reperfusion injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1879-0712
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
650
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
298-302
pubmed:dateRevised
2011-10-6
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
PTEN inhibitors cause a negative inotropic and chronotropic effect in mice.
pubmed:affiliation
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, N.I.H., Extramural