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PTEN, the Achilles' heel of myocardial ischaemia/reperfusion injury?

Mocanu, MM; Yellon, DM; (2007) PTEN, the Achilles' heel of myocardial ischaemia/reperfusion injury? BRIT J PHARMACOL , 150 (7) 833 - 838. 10.1038/sj.bjp.0707155. Gold open access

Abstract

Myocardial ischaemia/reperfusion injury leading to myocardial infarction is one of the most frequent causes of debilitation and death in man. Considerable research has been undertaken to investigate the possibility of reducing myocardial infarction and increasing cell survival by activating certain endogenous prosurvival signaling pathways. Thus, it has been established that the activation of the PI3K (Phosphoinositide-3 kinase)/Akt (Protein kinase B, PKB) signaling pathway is essential for protection against ischaemia/reperfusion injury. This pathway has been shown to be activated by mechanical procedures (e.g. pre and post conditioning) as well as by a number of pharmacological agents. Although the activation of this prosurvival signaling pathway induces the phosphorylation of a large number of substrates implicated in increased cell survival, when activated over a prolonged period this pathway can have detrimental consequences by facilitating unwanted growth and malignancies. Importantly PTEN (phosphatase and tensin homolog deleted on chromosome ten), is the main phosphatase which negatively regulates the PI3K/Akt pathway. In this review we discuss: a) the significance and the limitations of inhibiting PTEN in myocardial ischaemia/reperfusion injury; b) PTEN and its relationship to ischaemic preconditioning, c) the role of PTEN in the development of tolerance to chronic administration of drugs known to limit infarction by activating PI3K/Akt pathway when given acutely, and d) the possible role of PTEN in the ischaemic/reperfused diabetic heart. The experimental evidence discussed in this review illustrates the importance of PTEN inhibition in the protection of the heart against ischaemia/reperfusion injury.

Type:Article
Title:PTEN, the Achilles' heel of myocardial ischaemia/reperfusion injury?
Open access status:An open access publication
DOI:10.1038/sj.bjp.0707155
Publisher version:http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2013879/?tool=pubmed
Keywords:myocardium, ischaemia, reperfusion, infarction, Akt, PTEN, TUMOR-SUPPRESSOR GENE, REPERFUSION INJURY, TENSIN HOMOLOG, ISCHEMIA/REPERFUSION INJURY, PHOSPHOINOSITIDE-3 KINASE, ENHANCED PHOSPHORYLATION, SIGNALING PATHWAYS, INSULIN-RESISTANCE, DIABETIC HEART, POTENTIAL ROLE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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