{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:12:57Z","timestamp":1785921177132,"version":"3.56.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,11,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Sesn2 (Sestrin2) is a stress\u2010induced protein that provides protective effects during myocardial ischemia and reperfusion (I\/R) injury, while endoplasmic reticulum (ER) stress may be a pivotal mediator of I\/R injury. The goal of this study was to determine whether Sesn2\u2010mTOR (mammalian target of rapamycin) signaling regulates ER stress during myocardial I\/R.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In vivo cardiac I\/R was induced by ligation and subsequent release of the left anterior descending coronary artery in wild\u2010type (WT) and cardiac\u2010specific Sesn2 knockout\u00a0(Sesn2\n                      <jats:sup>\n                        <jats:italic toggle=\"no\">cKO<\/jats:italic>\n                      <\/jats:sup>\n                      ) mice. At 6\u2009hours and 24\u2009hours after reperfusion, cardiac function was evaluated, and heart samples were collected for analysis. I\/R induced cardiac ER stress and upregulated Sesn2 mRNA and protein levels. Inhibiting ER stress with 4\u2010phenylbutyric acid reduced infarct size by 37.5%, improved cardiac systolic function, and mitigated myocardial cell apoptosis post\u2010I\/R. Hearts from Sesn2\n                      <jats:sup>\n                        <jats:italic toggle=\"no\">cKO<\/jats:italic>\n                      <\/jats:sup>\n                      mice displayed increased susceptibility to ER stress during I\/R compared with WT. Notably, cardiac mTOR signaling was further increased in Sesn2\n                      <jats:sup>\n                        <jats:italic toggle=\"no\">cKO<\/jats:italic>\n                      <\/jats:sup>\n                      hearts compared with WT hearts during I\/R. In mice with cardiac Sesn2 deficiency, compared with WT, ER lumen was significantly expanded after tunicamycin\u2010induced ER stress, as assessed by transmission electron microscopy. Additionally, pharmacological inhibition of mTOR signaling with rapamycin improved cardiac function after tunicamycin treatment and significantly attenuated the unfolded protein response and apoptosis in WT and Sesn2\n                      <jats:sup>\n                        <jats:italic toggle=\"no\">cKO<\/jats:italic>\n                      <\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Sesn2 attenuates cardiac ER stress post\u2010I\/R injury via regulation of mTOR signaling. Thus, modulation of the mTOR pathway by Sesn2 could be a critical factor for maintaining cardiac ER homeostasis control during myocardial I\/R injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.035193","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T05:49:36Z","timestamp":1730699376000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Sestrin2 Attenuates Myocardial Endoplasmic Reticulum Stress and Cardiac Dysfunction During Ischemia\/Reperfusion Injury"],"prefix":"10.1161","volume":"13","author":[{"given":"Xuan","family":"Li","sequence":"first","affiliation":[{"name":"University of Mississippi Medical Center","place":["Jackson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center","place":["Jackson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-3071","authenticated-orcid":false,"given":"Alan J.","family":"Mouton","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center","place":["Jackson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-7109","authenticated-orcid":false,"given":"Ana C. M.","family":"Omoto","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center","place":["Jackson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4504-0607","authenticated-orcid":false,"given":"Alexandre A.","family":"da Silva","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center","place":["Jackson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussara M.","family":"do Carmo","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center","place":["Jackson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-4412","authenticated-orcid":false,"given":"Ji","family":"Li","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center","place":["Jackson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9867-5855","authenticated-orcid":false,"given":"John E.","family":"Hall","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center","place":["Jackson, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000152"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra071667"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.004046"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3245"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183707"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2014.10.032"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.06.006"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2199"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.7.982"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.4161\/15384101.2014.991572"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2011.43.5.032"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.8b04241"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28240"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00070-18"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00629.2014"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004954"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5233"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.028"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.10.019"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep09502"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700063R"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.03.019"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-258814"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101824"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00137.2011"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.169771"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-018-9932-0"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0066-09.2009"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045156"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101637"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0991"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.98"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0778-09.2009"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.01.005"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094545"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.682054"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000233317.70421.03"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0644fje"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.12659\/msm.898623"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.08.038"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.125773"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3025"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2016.1151581"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2672"},{"key":"e_1_3_1_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00929-2"},{"key":"e_1_3_1_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.03.003"},{"key":"e_1_3_1_48_2","doi-asserted-by":"publisher","DOI":"10.12997\/jla.2023.12.3.290"},{"key":"e_1_3_1_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.01.048"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.035193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:03:48Z","timestamp":1784113428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.035193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,5]]},"references-count":48,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2024,11,5]]}},"alternative-id":["10.1161\/JAHA.124.035193"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.035193","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,5]]},"assertion":[{"value":"2024-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e035193"}}