{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:46:04Z","timestamp":1791326764067,"version":"4.3.1"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2009,1,6]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Chronic stimulation of the \u03b2\n            <jats:sub>1<\/jats:sub>\n            -adrenoceptor (\u03b2\n            <jats:sub>1<\/jats:sub>\n            AR) plays a crucial role in the pathogenesis of heart failure; however, underlying mechanisms remain to be elucidated. The regulation by transcription factors cAMP response element-binding protein (CREB) and cyclic AMP response element modulator (CREM) represents a fundamental mechanism of cyclic AMP\u2013dependent gene control possibly implicated in \u03b2\n            <jats:sub>1<\/jats:sub>\n            AR-mediated cardiac deterioration.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We studied the role of CREM in \u03b2\n            <jats:sub>1<\/jats:sub>\n            AR-mediated cardiac effects, comparing transgenic mice with heart-directed expression of \u03b2\n            <jats:sub>1<\/jats:sub>\n            AR in the absence and presence of functional CREM. CREM inactivation protected from cardiomyocyte hypertrophy, fibrosis, and left ventricular dysfunction in \u03b2\n            <jats:sub>1<\/jats:sub>\n            AR-overexpressing mice. Transcriptome and proteome analysis revealed a set of predicted CREB\/CREM target genes including the cardiac ryanodine receptor, tropomyosin 1\u03b1, and cardiac \u03b1-actin as altered on the mRNA or protein level along with the improved phenotype in CREM-deficient \u03b2\n            <jats:sub>1<\/jats:sub>\n            AR-transgenic hearts.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            The results imply the regulation of genes by CREM as an important mechanism of \u03b2\n            <jats:sub>1<\/jats:sub>\n            AR-induced cardiac damage in mice.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.108.786533","type":"journal-article","created":{"date-parts":[[2008,12,23]],"date-time":"2008-12-23T01:59:49Z","timestamp":1229997589000},"page":"79-88","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Critical Role of Transcription Factor Cyclic AMP Response Element Modulator in \u03b2\n            <sub>1<\/sub>\n            -Adrenoceptor\u2013Mediated Cardiac Dysfunction"],"prefix":"10.1161","volume":"119","author":[{"given":"Geertje","family":"Lewin","sequence":"first","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Matus","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Basu","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Frebel","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian Pius","family":"Rohsbach","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Safronenko","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias Dodo","family":"Seidl","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Stu\u0308mpel","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Buchwalow","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Ko\u0308nig","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Lohse","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Schmitz","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Ulrich","family":"Mu\u0308ller","sequence":"additional","affiliation":[{"name":"From the Institute of Pharmacology and Toxicology (G.L., M.M., A.B., K.F., S.P.R., A.S., M.D.S., F.S., W.S., F.U.M.), Institute of Pathology (I.B.), and Core Unit Integrated Functional Genomics, Interdisciplinary Center for Clinical Studies (S.K.), University of Mu\u0308nster, Mu\u0308nster, Germany; and Rudolf-Virchow Center, DFG\u2013Center for Experimental Biomedicine (S.E.), and Institute of Pharmacology (M.J.L.), University of Wu\u0308rzburg, Wu\u0308rzburg, Germany. Dr Lewin is currently affiliated with the Fraunhofer..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","unstructured":"Colucci WS Braunwald E. Pathophysiology of heart failure. In: Braunwald E ed. Heart Disease. 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