title: Cardiac Hypertrophy Is Inhibited by a Local Pool of cAMP Regulated by Phosphodiesterase 2.
abstract: BACKGROUND
  Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodeling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A signaling seems to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with the ability to generate multiple functional outcomes in response to different extracellular stimuli with strict fidelity, a feature that relies on the spatial segregation of the cAMP pathway components in signaling microdomains.
  
  
  OBJECTIVE
  How individual cAMP microdomains affect cardiac pathophysiology remains largely to be established. The cAMP-degrading enzymes phosphodiesterases (PDEs) play a key role in shaping local changes in cAMP. Here we investigated the effect of specific inhibition of selected PDEs on cardiac myocyte hypertrophic growth.
  
  
  RESULTS
  Using pharmacological and genetic manipulation of PDE activity, we found that the rise in cAMP resulting from inhibition of PDE3 and PDE4 induces hypertrophy, whereas increasing cAMP levels via PDE2 inhibition is antihypertrophic. By real-time imaging of cAMP levels in intact myocytes and selective displacement of protein kinase A isoforms, we demonstrate that the antihypertrophic effect of PDE2 inhibition involves the generation of a local pool of cAMP and activation of a protein kinase A type II subset, leading to phosphorylation of the nuclear factor of activated T cells.
  
  
  CONCLUSIONS
  Different cAMP pools have opposing effects on cardiac myocyte cell size. PDE2 emerges as a novel key regulator of cardiac hypertrophy in vitro and in vivo, and its inhibition may have therapeutic applications.
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Anna
authors.initials: A
authors.lastname: Zoccarato
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Nicoletta C
authors.initials: NC
authors.lastname: Surdo
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Jan M
authors.initials: JM
authors.lastname: Aronsen
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Laura A
authors.initials: LA
authors.lastname: Fields
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Luisa
authors.initials: L
authors.lastname: Mancuso
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Giuliano
authors.initials: G
authors.lastname: Dodoni
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stangherlin
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Craig
authors.initials: C
authors.lastname: Livie
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: He
authors.initials: H
authors.lastname: Jiang
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Yuan Yan
authors.initials: YY
authors.lastname: Sin
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Frank
authors.initials: F
authors.lastname: Gesellchen
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Anna
authors.initials: A
authors.lastname: Terrin
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: George S
authors.initials: GS
authors.lastname: Baillie
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Nicklin
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Delyth
authors.initials: D
authors.lastname: Graham
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Szabo-Fresnais
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Judith
authors.initials: J
authors.lastname: Krall
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Fabrice
authors.initials: F
authors.lastname: Vandeput
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Movsesian
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Leonardo
authors.initials: L
authors.lastname: Furlan
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Veronica
authors.initials: V
authors.lastname: Corsetti
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Graham
authors.initials: G
authors.lastname: Hamilton
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Lefkimmiatis
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.).
authors.forename: Ivar
authors.initials: I
authors.lastname: Sjaastad
authors.affiliation: From the Institute of Neuroscience and Psychology (A.Z., L.A.F., A.S., C.L., H.J., F.G., A.T., G.H., M.Z.) and Institute of Cardiovascular and Medical Sciences (Y.Y.S., G.S.B., S.A.N., D.G.), University of Glasgow, Glasgow, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK (N.C.S., K.L., M.Z.); Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway (J.M.A., I.S.); Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy (L.M., G.D., A.T., L.F., V.C.); Cardiology Section, VA Salt Lake City Health Care System and Cardiovascular Medicine Division, University of Utah School of Medicine, Salt Lake City, UT (N.S.-F., J.K., F.V., M.M.); Bjorknes College, Oslo, Norway (J.M.A.); and BHF Centre of Research Excellence, Oxford, UK (K.L., M.Z.). manuela.zaccolo@dpag.ox.ac.uk.
authors.forename: Manuela
authors.initials: M
authors.lastname: Zaccolo
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005822:Genetic Vectors; D008297:Male; D021962:Membrane Microdomains / Q000201:enzymology; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000187:drug effects; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection
chemical_list: D050778:NFATC Transcription Factors; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; C517277:Pde2a protein, mouse; C517278:Pde2a protein, rat
keywords: cAMP; cyclic nucleotide; hypertrophy; phosphodiesterases 2; protein kinase A; signal transduction