{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:28:33Z","timestamp":1787758113741,"version":"build-2784847793"},"reference-count":84,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung Blood Institute","doi-asserted-by":"publisher","award":["HLR01152215"],"award-info":[{"award-number":["HLR01152215"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung Blood Institute","doi-asserted-by":"publisher","award":["HL1R01HL164491"],"award-info":[{"award-number":["HL1R01HL164491"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung Blood Institute","doi-asserted-by":"publisher","award":["F32HL152523"],"award-info":[{"award-number":["F32HL152523"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung Blood Institute","doi-asserted-by":"publisher","award":["K08HL177282"],"award-info":[{"award-number":["K08HL177282"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung Blood Institute","doi-asserted-by":"publisher","award":["R25DK140753"],"award-info":[{"award-number":["R25DK140753"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["899027"],"award-info":[{"award-number":["899027"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Free fatty acid receptor 4 (Ffar4) is a receptor for long-chain fatty acids that attenuates heart failure driven by increased afterload. Recent findings suggest that Ffar4 prevents ischaemic injury in brain, liver, and kidney, and therefore, we hypothesized that Ffar4 would attenuate cardiac ischaemic injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Using a mouse model of ischaemia-reperfusion (I\/R), we found in mice with systemic deletion of Ffar4 (Ffar4KO), loss of Ffar4 impaired the recovery of left ventricular systolic function post-I\/R with no effect on initial infarct size. To identify potential mechanistic explanations for the cardioprotective effects of Ffar4, we performed bulk RNAseq to compare the transcriptomes from wild-type (WT) and Ffar4KO infarcted myocardium 3-days post-I\/R. The transcriptome analysis identified the downregulation of several metabolic pathways suggesting impaired mitochondrial function in the infarcted Ffar4KO myocardium. Mechanistically, basal mitochondrial function and morphology were impaired in cardiac myocytes from Ffar4KO mice corroborating the results of the transcriptome analysis. Interestingly, phosphodiesterase 6c (Pde6c), which degrades cGMP, was the most upregulated gene in the Ffar4KO heart. Further, the soluble guanylyl cyclase stimulator, vericiguat, failed to increase cGMP in Ffar4KO cardiac myocytes, suggesting increased phosphodiesterase activity. Finally, cardiac myocyte-specific overexpression of Ffar4 in vivo and activation of Ffar4 in cardiac myocytes in vitro attenuated ischaemic\/hypoxic injury respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results define a novel protective role for Ffar4 in cardiac myocytes to attenuate systolic dysfunction and prevent ischaemic cardiomyopathy post I\/R by preserving mitochondrial function and activating cGMP signalling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag175","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:15:16Z","timestamp":1786706116000},"source":"Crossref","is-referenced-by-count":0,"title":["Free fatty acid receptor 4 in cardiac myocytes ameliorates ischaemic cardiomyopathy"],"prefix":"10.1093","author":[{"given":"Michael J","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]},{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota Medical School , Minneapolis, MN ,","place":["USA"]},{"name":"Lillehei Heart Institute, University of Minnesota Medical School , 4-156 CCRB, 2231 6th Street SE, Minneapolis, MN 55455 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara J","family":"Puccini","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Karachenets","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan J","family":"Gyberg","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanmugasundaram","family":"Pakkiriswami","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan K","family":"Sumera","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Gemilere","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie L","family":"Weir","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian L","family":"Torres","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota Medical School , Minneapolis, MN ,","place":["USA"]},{"name":"Lillehei Heart Institute, University of Minnesota Medical School , 4-156 CCRB, 2231 6th Street SE, Minneapolis, MN 55455 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chastity L","family":"Healy","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A","family":"Harsch","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Pennsylvania State University , 110 Chandlee Laboratory, University Park, PA 16802 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of Minnesota Medical School , 3-141 CCRB, 2231 6th Street SE, Minneapolis, MN 55414 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