{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:28:47Z","timestamp":1791818927175,"version":"4.3.4"},"reference-count":135,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009021","name":"Heart Research Australia","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100009021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in remote ischemic preconditioning (RIPC)-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by a 30-min transient blockade of the left coronary artery to simulate ischemia reperfusion (I\/R) injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I\/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC, respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant interleukin-6 (IL-6) treatment prior to I\/R increased in vitro autophagy in a dose-dependent manner, activating the Janus kinase\/signal transducers and activators of transcription (JAK-STAT) pathway without affecting the other kinase pathways, such as p38 mitogen-activated protein kinases (MAPK), and glycogen synthase kinase 3 Beta (GSK-3\u03b2) pathways. Prior to I\/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6\/JAK-STAT-dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.<\/jats:p>","DOI":"10.3390\/ijms21051692","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T03:13:28Z","timestamp":1583205208000},"page":"1692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Remote Ischemic Preconditioning Induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway"],"prefix":"10.3390","volume":"21","author":[{"given":"Muntasir","family":"Billah","sequence":"first","affiliation":[{"name":"Department of Cardiology, Kolling Institute of Medical Research, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia"},{"name":"Sydney Medical School Northern, University of Sydney, Sydney, NSW 2006, Australia"},{"name":"School of Life Sciences, Independent University Bangladesh, Dhaka 1229, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-6896","authenticated-orcid":false,"given":"Anisyah","family":"Ridiandries","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kolling Institute of Medical Research, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia"},{"name":"Sydney Medical School Northern, University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usaid K","family":"Allahwala","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kolling Institute of Medical Research, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia"},{"name":"Sydney Medical School Northern, University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshini","family":"Mudaliar","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kolling Institute of Medical Research, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Dona","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kolling Institute of Medical Research, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Hunyor","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kolling Institute of Medical Research, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3446-0323","authenticated-orcid":false,"given":"Levon M.","family":"Khachigian","sequence":"additional","affiliation":[{"name":"Vascular Biology and Translational Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinay","family":"Bhindi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kolling Institute of Medical Research, Northern Sydney Local Health District, St Leonards, NSW 2065, Australia"},{"name":"Sydney Medical School Northern, University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1161\/01.CIR.74.5.1124","article-title":"Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium","volume":"74","author":"Murry","year":"1986","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1161\/CIRCRESAHA.116.305348","article-title":"Molecular basis of cardioprotection: Signal transduction in ischemic pre-, post-, and remote conditioning","volume":"116","author":"Heusch","year":"2015","journal-title":"Circ. 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