{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:32:32Z","timestamp":1781105552034,"version":"3.54.1"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,9,16]]},"abstract":"<jats:p>\n                    Pim-1 kinase exerts potent cardioprotective effects in the myocardium downstream of AKT, but the participation of Pim-1 in cardiac hypertrophy requires investigation. Cardiac-specific expression of Pim-1 (Pim-WT) or the dominant-negative mutant of Pim-1 (Pim-DN) in transgenic mice together with adenoviral-mediated overexpression of these Pim-1 constructs was used to delineate the role of Pim-1 in hypertrophy. Transgenic overexpression of Pim-1 protects mice from pressure-overload-induced hypertrophy relative to wild-type controls as evidenced by improved hemodynamic function, decreased apoptosis, increases in antihypertrophic proteins, smaller myocyte size, and inhibition of hypertrophic signaling after challenge. Similarly, Pim-1 overexpression in neonatal rat cardiomyocyte cultures inhibits hypertrophy induced by endothelin-1. On the cellular level, hearts of Pim-WT mice show enhanced incorporation of BrdU into myocytes and a hypercellular phenotype compared to wild-type controls after hypertrophic challenge. In comparison, transgenic overexpression of Pim-DN leads to dilated cardiomyopathy characterized by increased apoptosis, fibrosis, and severely depressed cardiac function. Furthermore, overexpression of Pim-DN leads to reduced contractility as evidenced by reduced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient amplitude and decreased percentage of cell shortening in isolated myocytes. These data support a pivotal role for Pim-1 in modulation of hypertrophy by impacting responses on molecular, cellular, and organ levels.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0709135105","type":"journal-article","created":{"date-parts":[[2008,9,10]],"date-time":"2008-09-10T21:43:41Z","timestamp":1221083021000},"page":"13889-13894","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":58,"title":["Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload"],"prefix":"10.1073","volume":"105","author":[{"given":"John A.","family":"Muraski","sequence":"first","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberlee M.","family":"Fischer","sequence":"additional","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitao","family":"Wu","sequence":"additional","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"Cottage","sequence":"additional","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pearl","family":"Quijada","sequence":"additional","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Mason","sequence":"additional","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabana","family":"Din","sequence":"additional","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Gude","sequence":"additional","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Roberto","family":"Alvarez","sequence":"additional","affiliation":[{"name":"*San Diego State Heart Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Rota","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Boston, MA 00311;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kajstura","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Boston, MA 00311;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeping","family":"Wang","sequence":"additional","affiliation":[{"name":"Invitrogen Corporation, Hopkinton, MA 01748;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Invitrogen Corporation, Hopkinton, MA 01748;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongen","family":"Chen","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"MacDonnel","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Magnuson","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, Washington State University, Pullman, WA 99164; 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