{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:41:05Z","timestamp":1791358865216,"version":"4.3.1"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Prostaglandin E2 (PGE\n              <jats:sub>2<\/jats:sub>\n              ) EP receptors EP3 and EP4 signal via decreased and increased cAMP production, respectively. Previously, we reported that cardiomyocyte-specific EP4 knockout mice develop dilated cardiomyopathy with reduced ejection fraction. Thus, we hypothesized that PGE\n              <jats:sub>2<\/jats:sub>\n              increases contractility via EP4 but decreases contractility via EP3.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              The effects of PGE\n              <jats:sub>2<\/jats:sub>\n              and the EP1\/EP3 agonist sulprostone on contractility were examined in the mouse Langendorff preparation and in adult mouse cardiomyocytes. Isolated hearts of adult male C57Bl\/6 mice were perfused with PGE\n              <jats:sub>2<\/jats:sub>\n              (10\n              <jats:sup>\u22126<\/jats:sup>\n              M) or sulprostone (10\n              <jats:sup>\u22126<\/jats:sup>\n              M) and compared with vehicle. Both PGE\n              <jats:sub>2<\/jats:sub>\n              and sulprostone decreased +dp\/dt (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01) and left ventricular developed pressure (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) with reversal by an EP3 antagonist. In contrast, the EP4 agonist had the opposite effect. Adult mouse cardiomyocytes contractility was also reduced after treatment with either PGE\n              <jats:sub>2<\/jats:sub>\n              or sulprostone for 10 minutes. We then examined the acute effects of PGE\n              <jats:sub>2<\/jats:sub>\n              , sulprostone, and the EP4 agonist on expression of phosphorylated phospholamban and sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              -ATPase 2a in adult mouse cardiomyocytes using Western blot. Treatment with either PGE\n              <jats:sub>2<\/jats:sub>\n              or sulprostone decreased expression of phosphorylated phospholamban corrected to total phospholamban, whereas treatment with the EP4 agonist had the opposite effect. Sarcoendoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              -ATPase 2a expression was unaffected. Finally, we examined the effect of these compounds in vivo using pressure\u2013volume loops. Both PGE\n              <jats:sub>2<\/jats:sub>\n              and sulprostone decreased +dp\/dt, whereas the EP4 agonist increased +dp\/dt.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in phospholamban phosphorylation and has relevance to detrimental effects of inflammation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.116.003291","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T03:04:01Z","timestamp":1470711841000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor"],"prefix":"10.1161","volume":"9","author":[{"given":"Xiaosong","family":"Gu","sequence":"first","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Department of Internal Medicine (X.G., J.X., L.Z., T.B., X.-P.Y., P.H.) and Department of Physiology (T.B., P.H.), Wayne State University School of Medicine, Detroit, MI; Department of Public Health Sciences (E.P.), Henry Ford Hospital, Detroit, MI; and Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Department of Internal Medicine (X.G., J.X., L.Z., T.B., X.-P.Y., P.H.) and Department of Physiology (T.B., P.H.), Wayne State University School of Medicine, Detroit, MI; Department of Public Health Sciences (E.P.), Henry Ford Hospital, Detroit, MI; and Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Department of Internal Medicine (X.G., J.X., L.Z., T.B., X.-P.Y., P.H.) and Department of Physiology (T.B., P.H.), Wayne State University School of Medicine, Detroit, MI; Department of Public Health Sciences (E.P.), Henry Ford Hospital, Detroit, MI; and Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Bryson","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Department of Internal Medicine (X.G., J.X., L.Z., T.B., X.-P.Y., P.H.) and Department of Physiology (T.B., P.H.), Wayne State University School of Medicine, Detroit, MI; Department of Public Health Sciences (E.P.), Henry Ford Hospital, Detroit, MI; and Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Department of Internal Medicine (X.G., J.X., L.Z., T.B., X.-P.Y., P.H.) and Department of Physiology (T.B., P.H.), Wayne State University School of Medicine, Detroit, MI; Department of Public Health Sciences (E.P.), Henry Ford Hospital, Detroit, MI; and Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Peterson","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Department of Internal Medicine (X.G., J.X., L.Z., T.B., X.-P.Y., P.H.) and Department of Physiology (T.B., P.H.), Wayne State University School of Medicine, Detroit, MI; Department of Public Health Sciences (E.P.), Henry Ford Hospital, Detroit, MI; and Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Harding","sequence":"additional","affiliation":[{"name":"From the Hypertension and Vascular Research Division, Department of Internal Medicine (X.G., J.X., L.Z., T.B., X.-P.Y., P.H.) and Department of Physiology (T.B., P.H.), Wayne State University School of Medicine, Detroit, MI; Department of Public Health Sciences (E.P.), Henry Ford Hospital, Detroit, MI; and Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00746.2009"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.102590"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805806106"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2003.09.002"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069832"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1385\/1-59745-214-9:271"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.138"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1117862109"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-014-1012-2"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.1.H117"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-013-2905-x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/aas.12022"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn312"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-6980(02)00014-X"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000128046.54681.97"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2011.01.003"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e318145ae2e"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.58.6.1279"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02640-0"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98381-X"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.22.15719"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-3278(96)90018-6"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2016.02.019"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.02.029"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.116.003291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:23:31Z","timestamp":1715563411000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.116.003291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.116.003291"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.116.003291","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8]]},"assertion":[{"value":"2015-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e003291"}}