{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T05:00:49Z","timestamp":1780722049562,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["3160298"],"award-info":[{"award-number":["3160298"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Reperfusion Injury Salvage Kinase (RISK) pathway is considered the main pro\u2010survival kinase cascade mediating the ischaemic preconditioning (IPC) cardioprotective effect. To assess the role of PI3K\u2010Akt, its negative regulator PTEN and other pro\u2010survival proteins such as ERK and STAT3 in the context of IPC, C57BL\/6 mouse hearts were retrogradely perfused in a Langendorff system and subjected to 4 cycles of 5 min. ischaemia and 5 min. reperfusion prior to 35 min. of global ischaemia and 120 min. of reperfusion. Wortmannin, a PI3K inhibitor, was administered either at the stabilization period or during reperfusion. Infarct size was assessed using triphenyl tetrazolium staining, and phosphorylation levels of Akt, PTEN, ERK, GSK3\u03b2 and STAT3 were evaluated using Western blot analyses. IPC reduced infarct size in hearts subjected to lethal ischaemia and reperfusion, but this effect was lost in the presence of Wortmannin, whether it was present only during preconditioning or only during early reperfusion. IPC increased the levels of Akt phosphorylation during both phases and this effect was fully abrogated by PI3K, whilst its downstream GSK3\u03b2 was phosphorylated only during the trigger phase after IPC. Both PTEN and STAT3 were phosphorylated during both phases after IPC, but this was PI3K independent. IPC increases ERK phosphorylation during both phases, being only PI3K\u2010dependent during the IPC phase. In conclusion, PI3K\u2010Akt plays a major role in IPC\u2010induced cardioprotection. However, PTEN, ERK and STAT3 are also phosphorylated by IPC through a PI3K\u2010independent pathway, suggesting that cardioprotection is mediated through more than one cell signalling cascade.<\/jats:p>","DOI":"10.1111\/jcmm.13394","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T03:36:42Z","timestamp":1511235402000},"page":"926-935","source":"Crossref","is-referenced-by-count":41,"title":["Role of PI3K in myocardial ischaemic preconditioning: mapping pro\u2010survival cascades at the trigger phase and at reperfusion"],"prefix":"10.1111","volume":"22","author":[{"given":"Xavier","family":"Rossello","sequence":"first","affiliation":[{"name":"The Hatter Cardiovascular Institute University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime A","family":"Riquelme","sequence":"additional","affiliation":[{"name":"The Hatter Cardiovascular Institute University College London London UK"},{"name":"Advanced Center for Chronic Diseases (ACCDiS) Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-4980","authenticated-orcid":false,"given":"Sean M","family":"Davidson","sequence":"additional","affiliation":[{"name":"The Hatter Cardiovascular Institute University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-9320","authenticated-orcid":false,"given":"Derek M","family":"Yellon","sequence":"additional","affiliation":[{"name":"The Hatter Cardiovascular Institute University College London London 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