{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:20:57Z","timestamp":1787016057764,"version":"build-2736575974"},"reference-count":72,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec>\n                    <jats:title>New Findings<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:bold>What is the central question of this study?<\/jats:bold>\n                          <\/jats:p>\n                          <jats:p>Can short\u2010term high\u2010intensity interval training (HIIT) contribute to the reduction of ischaemia\u2013reperfusion (IR) injury by enhancing the levels of Klotho and its related axes, including myocardial TRPC6 expression, and antioxidant defence as novel possible mechanisms of exercise\u2010induced cadioprotection (EICP) against IR injury?<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:bold>What is the main finding and its importance?<\/jats:bold>\n                          <\/jats:p>\n                          <jats:p>The increase of plasma and myocardial levels of Klotho as a result of preconditioning with HIIT and prevention of a significant reduction of Klotho during IR injury can promote cardioprotection and reduce damage by attenuating myocardial TRPC6 expression and increasing antioxidant defence. The present findings may provide a new mechanism in EICP and IR injury, and provide the knowledge to develop preventive and therapeutic approaches.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Cardiovascular disease, especially coronary artery disease, remains a major cause of morbidity and mortality in the world, and ischaemia\u2013reperfusion (IR) insult is the main pathological cause leading to death. Exercise training is associated with a reduced risk of cardiovascular disease and the development of cardioprotection against IR injury. Therefore, the purpose of this study was to investigate the effect of preconditioning with high\u2010intensity interval training (HIIT) on myocardial and plasma levels of Klotho and its related axes as novel mechanisms of exercise\u2010induced cardioprotection against IR injury. Seventy male Wistar rats were randomly divided into five groups of control, HIIT, sham, IR and HIIT group that underwent IR injury (H\u2010IR). The training group performed five sessions of HIIT on the treadmill. The cardiac IR injury was induced by ligation of the left anterior descending coronary artery for 30\u00a0min followed by 24\u00a0h reperfusion. Infarct size and histopathological assessment of cardiac tissues were determined through Evans Blue\u2013triphenyltetrazolium chloride and haematoxylin\u2013eosin staining, respectively. We investigated lipid peroxidation and markers of cardiac injury, antioxidant enzymes and the plasma levels of Klotho using enzyme\u2010linked immunosorbent assays. Also, myocardial levels of Klotho and TRPC6 expression were determined by western blot assays. The results demonstrated a significant increase in myocardial and plasma levels of Klotho following HIIT and a significant decrease during IR injury. Myocardial TRPC6 channel expression increased following IR. HIIT also prevented a significant reduction of Klotho during IR and consequently reduced the expression of the TRPC6 channel in the H\u2010IR group compared with the IR group. Furthermore, HIIT decreased the infarct size, cardiac injury, lipid peroxidation, lactate dehydrogenase, creatine kinase myocardial band and cardiac troponin\u2010I, and improved total antioxidant capacity and catalase, superoxide dismutase and glutathione peroxidase activities following IR injury. The findings of the present study suggest that HIIT improves cardioprotection against IR injury and reduces cardiac damages through an increase in myocardial and plasma levels of Klotho and its related axes (TRPC6 and antioxidant defence). These findings can help to develop preventive and therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/ep087994","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T02:58:04Z","timestamp":1581562684000},"page":"652-665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["High\u2010intensity interval training increases myocardial levels of Klotho and protects the heart against ischaemia\u2013reperfusion injury"],"prefix":"10.1113","volume":"105","author":[{"given":"Maral","family":"Ramez","sequence":"first","affiliation":[{"name":"Department of Exercise physiology Faculty of Physical Education and Sport Sciences, Kharazmi University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Ramezani","sequence":"additional","affiliation":[{"name":"Physiology Research Center and Physiology Department Faculty of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farinaz","family":"Nasirinezhad","sequence":"additional","affiliation":[{"name":"Physiology Research Center and Physiology Department Faculty of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1096-5792","authenticated-orcid":false,"given":"Hamid","family":"Rajabi","sequence":"additional","affiliation":[{"name":"Department of Exercise physiology Faculty of Physical Education and Sport Sciences, Kharazmi University  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00189"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023570"},{"issue":"1","key":"e_1_2_9_4_1","first-page":"71","article-title":"Mechanisms involved in exercise\u2010induced cardioprotection: A systematic review","volume":"105","author":"Borges J. P.","year":"2015","journal-title":"Arquivos Brasileiros de Cardiologia"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.vh.2016.02.005"},{"issue":"8","key":"e_1_2_9_6_1","first-page":"701","article-title":"Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease","volume":"13","author":"Corsetti G.","year":"2016","journal-title":"Journal of Geriatric Cardiology"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00068-007-7152-z"},{"issue":"9","key":"e_1_2_9_8_1","first-page":"1270","article-title":"Cardioprotective effect of high intensity interval training and nitric oxide metabolites (NO2\u2212, NO3\u2212)","volume":"44","author":"Fallahi A.","year":"2015","journal-title":"Iranian Journal of Public Health"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46122"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0142"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00004.2011"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-102541"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-020-01380-w"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063825"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.224725"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611079104"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJR.0b013e3281eacef1"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.328"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.73"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14933"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01231.2007"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.27.61"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.03.010"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.15280\/jlm.2015.5.1.1"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2009.02.005"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-009-0722-7"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e318231c037"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.053405"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060658"},{"issue":"5","key":"e_1_2_9_30_1","first-page":"7351","article-title":"Klotho: A novel and early biomarker of acute kidney injury after cardiac valve replacement surgery in adults","volume":"8","author":"Liu Y.\u2010J.","year":"2015","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3669"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/757469"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v6.i12.1262"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00429.2013"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2016.09.001"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.07.009"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0260-x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000086500"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.104828"},{"issue":"4","key":"e_1_2_9_40_1","first-page":"e38","article-title":"Heart disease and stroke statistics\u20102016 update a report from the American Heart Association","volume":"133","author":"Mozaffarian D.","year":"2016","journal-title":"Circulation"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2007"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0594.2010.00612.x"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.03.043"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.305873"},{"key":"e_1_2_9_45_1","first-page":"189","article-title":"Klotho: The protein of faith","volume":"7","author":"Patrikios I.","year":"2017","journal-title":"EC Neurology"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.135"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.02.006"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00030.2013"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.11.021"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00957.2011"},{"key":"e_1_2_9_51_1","first-page":"237","article-title":"The effect of high intensity interval training on cardioprotection against ischemia\u2010reperfusion injury in Wistar rats","volume":"14","author":"Rahimi M.","year":"2015","journal-title":"EXCLI Journal"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-019-1090-7"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40279-015-0321-z"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2006.05.020"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003319710385338"},{"issue":"1","key":"e_1_2_9_56_1","first-page":"001","article-title":"Effects of aerobic exercise training on s\u2010Klotho in young and elderly","volume":"1","author":"Saghiv M.","year":"2015","journal-title":"JJ Physiology"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00894-9"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8035"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00313.2007"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082968"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000124224.48962.32"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156860"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.12.002"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.16-108"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00796.x"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2008.10.002"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20060368"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2240"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2013-1079"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509039200"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.03.138"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.244"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7961940"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FEP087994","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP087994","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP087994","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP087994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T12:47:46Z","timestamp":1694004466000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP087994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,17]]},"references-count":72,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1113\/EP087994"],"URL":"https:\/\/doi.org\/10.1113\/ep087994","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,17]]},"assertion":[{"value":"2019-07-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}