{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:02:11Z","timestamp":1790024531187,"version":"4.0.1"},"reference-count":40,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The unfolded protein response (UPR) plays a pivotal role in ischemia\u2013reperfusion (I\/R) injury in various organs such as heart, brain, and liver. Sodium 4-phenylbutyrate (PBA) reportedly acts as a chemical chaperone that reduces UPR. In the present study, we evaluated the effect of PBA on reducing the UPR and protecting against myocardial I\/R injury in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Male C57BL\/6 mice were subjected to 30-minute myocardial I\/R, and were treated with phosphate-buffered saline (as a vehicle) or PBA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>At 4 hours after reperfusion, mice treated with PBA had reduced serum cardiac troponin I levels and numbers of apoptotic cells in left ventricles (LVs) in myocardial I\/R. Infarct size had also reduced in mice treated with PBA at 48 hours after reperfusion. At 2 hours after reperfusion, UPR markers, including eukaryotic initiation of the factor 2\u03b1-subunit, activating transcription factor-6, inositol-requiring enzyme-1, glucose-regulated protein 78, CCAAT\/enhancer-binding protein (C\/EBP) homologous protein, and caspase-12, were significantly increased in mice treated with vehicle compared to sham-operated mice. Administration of PBA significantly reduced the I\/R-induced increases of these markers. Cardiac function and dimensions were assessed at 21 days after I\/R. Sodium 4-phenylbutyrate dedicated to the improvement of cardiac parameters deterioration including LV end-diastolic diameter and LV fractional shortening. Consistently, PBA reduced messenger RNA expression levels of cardiac remodeling markers such as collagen type 1\u03b11, brain natriuretic peptide, and \u03b1 skeletal muscle actin in LV at 21 days after I\/R.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Unfolded protein response mediates myocardial I\/R injury. Administration of PBA reduces the UPR, apoptosis, infarct size, and preserved cardiac function. Hence, PBA may be a therapeutic option to attenuate myocardial I\/R injury in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1074248416679308","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T21:00:29Z","timestamp":1480626029000},"page":"283-292","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response"],"prefix":"10.1177","volume":"22","author":[{"given":"Osamu","family":"Takatori","sequence":"first","affiliation":[{"name":"Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Usui","sequence":"additional","affiliation":[{"name":"Department of Disease Control and Homeostasis, Kanazawa 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