{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:10:09Z","timestamp":1788455409967,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2016,7,8]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Mitogen-activated protein kinase (MAPK) signaling regulates the growth response of the adult myocardium in response to increased cardiac workload or pathological insults. The dual-specificity phosphatases (DUSPs) are critical effectors, which dephosphorylate the MAPKs to control the basal tone, amplitude, and duration of MAPK signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>To examine DUSP8 as a regulator of MAPK signaling in the heart and its impact on ventricular and cardiac myocyte growth dynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      <jats:italic>Dusp8<\/jats:italic>\n                      gene\u2013deleted mice and transgenic mice with inducible expression of DUSP8 in the heart were used here to investigate how this MAPK-phosphatase might regulate intracellular signaling and cardiac growth dynamics in vivo.\n                      <jats:italic>Dusp8<\/jats:italic>\n                      gene\u2013deleted mice were mildly hypercontractile at baseline with a cardiac phenotype of concentric ventricular remodeling, which protected them from progressing towards heart failure in 2 surgery-induced disease models. Cardiac-specific overexpression of DUSP8 produced spontaneous eccentric remodeling and ventricular dilation with heart failure. At the cellular level, adult cardiac myocytes from\n                      <jats:italic>Dusp8<\/jats:italic>\n                      gene\u2013deleted mice were thicker and shorter, whereas DUSP8 overexpression promoted cardiac myocyte lengthening with a loss of thickness. Mechanistically, activation of extracellular signal\u2013regulated kinases 1\/2 were selectively increased in\n                      <jats:italic>Dusp8<\/jats:italic>\n                      gene\u2013deleted hearts at baseline and following acute pathological stress stimulation, whereas p38 MAPK and c-Jun N-terminal kinases were mostly unaffected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>These results indicate that DUSP8 controls basal and acute stress-induced extracellular signal\u2013regulated kinases 1\/2 signaling in adult cardiac myocytes that then alters the length\u2013width growth dynamics of individual cardiac myocytes, which further alters contractility, ventricular remodeling, and disease susceptibility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.115.308238","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T23:54:43Z","timestamp":1464220483000},"page":"249-260","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["DUSP8 Regulates Cardiac Ventricular Remodeling by Altering ERK1\/2 Signaling"],"prefix":"10.1161","volume":"119","author":[{"given":"Ruijie","family":"Liu","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, University of Cincinnati (R.L., J.H.v.B., A.J.Y., R.J.V., M.M., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH; and Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota, St. Paul (J.H.v.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jop H.","family":"van Berlo","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, University of Cincinnati (R.L., J.H.v.B., A.J.Y., R.J.V., M.M., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH; and Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota, St. Paul (J.H.v.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen J.","family":"York","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, University of Cincinnati (R.L., J.H.v.B., A.J.Y., R.J.V., M.M., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH; and Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota, St. Paul (J.H.v.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Vagnozzi","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, University of Cincinnati (R.L., J.H.v.B., A.J.Y., R.J.V., M.M., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH; and Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota, St. Paul (J.H.v.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Maillet","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, University of Cincinnati (R.L., J.H.v.B., A.J.Y., R.J.V., M.M., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH; and Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota, St. Paul (J.H.v.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, University of Cincinnati (R.L., J.H.v.B., A.J.Y., R.J.V., M.M., J.D.M.) and Howard Hughes Medical Institute (J.D.M.), Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH; and Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota, St. Paul 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