{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:52:41Z","timestamp":1788407561806,"version":"build-2803163510"},"reference-count":66,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL154720,R01DK122796,R01HL133900"],"award-info":[{"award-number":["R01HL154720,R01DK122796,R01HL133900"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Defense Grant","award":["W81XWH2110032"],"award-info":[{"award-number":["W81XWH2110032"]}]},{"name":"2022 International Anesthesia Research Society Mentored Research Award","award":["Mentored Research Award"],"award-info":[{"award-number":["Mentored Research Award"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL155950"],"award-info":[{"award-number":["R01HL155950"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"American Lung Association Catalyst Award","award":["CA-622265"],"award-info":[{"award-number":["CA-622265"]}]},{"name":"Natural Science Foundation of Hunan Province Grant","award":["2018JJ3736"],"award-info":[{"award-number":["2018JJ3736"]}]},{"name":"Young Talent Foundation of Hunan Province Grant","award":["2021RC3034"],"award-info":[{"award-number":["2021RC3034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,8]]},"abstract":"<jats:p>\n                    Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global\n                    <jats:italic>Ent1<\/jats:italic>\n                    or\n                    <jats:italic>Ent2<\/jats:italic>\n                    deletion showed cardioprotection only in\n                    <jats:italic>\n                      Ent1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Moreover, studies with tissue-specific\n                    <jats:italic>Ent<\/jats:italic>\n                    deletion revealed that mice with myocyte-specific\n                    <jats:italic>Ent1<\/jats:italic>\n                    deletion (\n                    <jats:italic>\n                      Ent1\n                      <jats:sup>loxP\/loxP<\/jats:sup>\n                    <\/jats:italic>\n                    Myosin Cre\n                    <jats:sup>+<\/jats:sup>\n                    mice) experienced smaller infarct sizes. Measurements of cardiac adenosine levels demonstrated that postischemic elevations of adenosine persisted during reperfusion after targeting ENTs. Finally, studies in mice with global or myeloid-specific deletion of the\n                    <jats:italic>Adora2b<\/jats:italic>\n                    adenosine receptor (\n                    <jats:italic>\n                      Adora2b\n                      <jats:sup>loxP\/loxP<\/jats:sup>\n                    <\/jats:italic>\n                    LysM Cre\n                    <jats:sup>+<\/jats:sup>\n                    mice) implied that Adora2b signaling on myeloid-inflammatory cells in cardioprotection provided by ENT inhibition. These studies reveal a previously unrecognized role for myocyte-specific ENT1 in cardioprotection by enhancing myeloid-dependent Adora2b signaling during reperfusion. Extension of these findings implicates adenosine transporter inhibitors in cardioprotection against ischemia and reperfusion injury.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.166011","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T14:01:32Z","timestamp":1686146492000},"source":"Crossref","is-referenced-by-count":24,"title":["Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-7923","authenticated-orcid":true,"given":"Wei","family":"Ruan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Critical Care and Pain Medicine, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA."},{"name":"Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, 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