{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:36:50Z","timestamp":1780054610611,"version":"3.54.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,7,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Ischemia\/reperfusion injury (IRI) is one of the most predominant complications of ischemic heart disease. Gastrin has emerged as a regulator of cardiovascular function, playing a key protective role in hypoxia. Serum gastrin levels are increased in patients with myocardial infarction, but the pathophysiogical significance of this finding is unknown. The purpose of this study was to determine whether and how gastrin protects cardiac myocytes from IRI.<\/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              Adult male Sprague\u2010Dawley rats were used in the experiments. The hearts in living rats or isolated Langendorff\u2010perfused rat hearts were subjected to ischemia followed by reperfusion to induce myocardial IRI. Gastrin, alone or with an antagonist, was administered before the induction of myocardial IRI. We found that gastrin improved myocardial function and reduced the expression of myocardial injury markers, infarct size, and cardiomyocyte apoptosis induced by IRI. Gastrin increased the phosphorylation levels of\n              <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n              1\/2 (extracellular signal\u2010regulated kinase 1\/2), AKT (protein kinase B), and\n              <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>\n              3 (signal transducer and activator of transcription 3), indicating its ability to activate the\n              <jats:styled-content style=\"fixed-case\">RISK<\/jats:styled-content>\n              (reperfusion injury salvage kinase) and\n              <jats:styled-content style=\"fixed-case\">SAFE<\/jats:styled-content>\n              (survivor activating factor enhancement) pathways. The presence of inhibitors of\n              <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n              1\/2,\n              <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>\n              , or\n              <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>\n              3 abrogated the gastrin\u2010mediated protection. The protective effect of gastrin was via CCK2R (cholecystokinin 2 receptor) because the\n              <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>\n              2R blocker\n              <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\n              988 prevented the gastrin\u2010mediated protection of the heart with IRI. Moreover, we found a negative correlation between serum levels of cardiac troponin I and gastrin in patients with unstable angina pectoris undergoing percutaneous coronary intervention, suggesting a protective effect of gastrin in human cardiomyocytes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These results indicate that gastrin can reduce myocardial IRI by activation of the\n              <jats:styled-content style=\"fixed-case\">RISK<\/jats:styled-content>\n              and\n              <jats:styled-content style=\"fixed-case\">SAFE<\/jats:styled-content>\n              pathways.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.005171","type":"journal-article","created":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T09:15:49Z","timestamp":1531386949000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Gastrin Protects Against Myocardial Ischemia\/Reperfusion Injury via Activation of RISK (Reperfusion Injury Salvage Kinase) and SAFE (Survivor Activating Factor Enhancement) Pathways"],"prefix":"10.1161","volume":"7","author":[{"given":"Xiaoli","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongchuan","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Cardiology North Sichuan Medical College First Affiliated Hospital Nanchong Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukai","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinquan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Eric","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chongqing Institute of Cardiology Daping Hospital Third Military Medical University Chongqing China"},{"name":"Cardiovascular Research Center &amp; 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