J D Molkentin

Summary

Affiliation: Children's Hospital Medical Center
Country: USA

Publications

  1. ncbi A friend within the heart: natriuretic peptide receptor signaling
    Jeffery D Molkentin
    Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    J Clin Invest 111:1275-7. 2003
  2. ncbi Cytoplasmic signaling pathways that regulate cardiac hypertrophy
    J D Molkentin
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229 3039, USA
    Annu Rev Physiol 63:391-426. 2001
  3. ncbi The transcription factor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes
    Q Liang
    Department of Pediatrics, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 21:7460-9. 2001
  4. ncbi Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy
    T Taigen
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Proc Natl Acad Sci U S A 97:1196-201. 2000
  5. ncbi The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo
    O F Bueno
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio, USA
    Circ Res 88:88-96. 2001
  6. ncbi Hypertrophic defect unmasked by calcineurin expression in asymptomatic tropomodulin overexpressing transgenic mice
    M A Sussman
    The Children s Hospital and Research Foundation, Division of Molecular Cardiovascular Biology, Room 3033, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Cardiovasc Res 46:90-101. 2000
  7. ncbi Calcineurin and beyond: cardiac hypertrophic signaling
    J D Molkentin
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Circ Res 87:731-8. 2000
  8. ncbi Calcineurin promotes protein kinase C and c-Jun NH2-terminal kinase activation in the heart. Cross-talk between cardiac hypertrophic signaling pathways
    L J De Windt
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 275:13571-9. 2000
  9. ncbi Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo
    L J De Windt
    Divisions of Molecular Cardiovascular Biology and Cardiology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 98:3322-7. 2001
  10. ncbi Enhanced Ca2+ channel currents in cardiac hypertrophy induced by activation of calcineurin-dependent pathway
    A Yatani
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
    J Mol Cell Cardiol 33:249-59. 2001

Collaborators

Detail Information

Publications99

  1. ncbi A friend within the heart: natriuretic peptide receptor signaling
    Jeffery D Molkentin
    Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    J Clin Invest 111:1275-7. 2003
  2. ncbi Cytoplasmic signaling pathways that regulate cardiac hypertrophy
    J D Molkentin
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229 3039, USA
    Annu Rev Physiol 63:391-426. 2001
    ..Each of these signaling pathways has been implicated as a hypertrophic transducer, which collectively suggests an emerging paradigm whereby multiple pathways operate in concert to orchestrate a hypertrophic response..
  3. ncbi The transcription factor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes
    Q Liang
    Department of Pediatrics, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 21:7460-9. 2001
    ....
  4. ncbi Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy
    T Taigen
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Proc Natl Acad Sci U S A 97:1196-201. 2000
    ....
  5. ncbi The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo
    O F Bueno
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio, USA
    Circ Res 88:88-96. 2001
    ....
  6. ncbi Hypertrophic defect unmasked by calcineurin expression in asymptomatic tropomodulin overexpressing transgenic mice
    M A Sussman
    The Children s Hospital and Research Foundation, Division of Molecular Cardiovascular Biology, Room 3033, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Cardiovasc Res 46:90-101. 2000
    ..Dilation and hypertrophy often occur concurrently in cardiomyopathy, yet the interaction between these two functionally distinct conditions remains unknown...
  7. ncbi Calcineurin and beyond: cardiac hypertrophic signaling
    J D Molkentin
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Circ Res 87:731-8. 2000
    ....
  8. ncbi Calcineurin promotes protein kinase C and c-Jun NH2-terminal kinase activation in the heart. Cross-talk between cardiac hypertrophic signaling pathways
    L J De Windt
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 275:13571-9. 2000
    ..Collectively, these data indicate that calcineurin hypertrophic signaling is interconnected with PKCalpha, theta, and JNK in the heart, while PKCepsilon, beta, lambda, p38, and ERK1/2 are not involved in calcineurin-mediated hypertrophy...
  9. ncbi Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo
    L J De Windt
    Divisions of Molecular Cardiovascular Biology and Cardiology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 98:3322-7. 2001
    ..These results provide genetic evidence implicating calcineurin as an important mediator of the cardiac hypertrophic response in vivo...
  10. ncbi Enhanced Ca2+ channel currents in cardiac hypertrophy induced by activation of calcineurin-dependent pathway
    A Yatani
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
    J Mol Cell Cardiol 33:249-59. 2001
    ..Taken together these data suggest that chronic activation of calcineurin is associated with myocyte hypertrophy and a secondary enhancement of intracellular Ca2+ handling that is tied to the hypertrophy response itself...
  11. ncbi The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo
    Q Liang
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 276:30245-53. 2001
    ..Expression of GATA4-engrailed blocked GATA4- and GATA6-directed transcriptional responses and agonist-induced cardiomyocyte hypertrophy, demonstrating that cardiac-expressed GATA factors are necessary mediators of this process...
  12. ncbi Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein
    D S Sohal
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio, USA
    Circ Res 89:20-5. 2001
    ....
  13. ncbi Direct activation of a GATA6 cardiac enhancer by Nkx2.5: evidence for a reinforcing regulatory network of Nkx2.5 and GATA transcription factors in the developing heart
    J D Molkentin
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, 45229 3039, USA
    Dev Biol 217:301-9. 2000
    ..These studies demonstrate that GATA6 is a direct target gene for Nkx2.5 in the developing heart and reveal a mutually reinforcing regulatory network of Nkx2.5 and GATA transcription factors during cardiogenesis...
  14. ncbi Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy
    B J Aronow
    Department of Developmental Biology, Children s Hospital Research Center, Cincinnati, OH 45229, USA
    Physiol Genomics 6:19-28. 2001
    ....
  15. ncbi Calcineurin enhances MAPK phosphatase-1 expression and p38 MAPK inactivation in cardiac myocytes
    H W Lim
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 276:15913-9. 2001
    ..These data suggest that calcineurin enhances MKP-1 expression in cardiac myocytes, which is associated with p38 inactivation...
  16. ncbi The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression
    J D Molkentin
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    J Biol Chem 275:38949-52. 2000
  17. ncbi Pathogenesis of dilated cardiomyopathy: molecular, structural, and population analyses in tropomodulin-overexpressing transgenic mice
    M A Sussman
    Division of Molecular Cardiovascular Biology, Children s Hospital and Research Foundation, Cincinnati, Ohio 45229, USA
    Am J Pathol 155:2101-13. 1999
    ....
  18. ncbi MEF2B is a component of a smooth muscle-specific complex that binds an A/T-rich element important for smooth muscle myosin heavy chain gene expression
    Y Katoh
    Section of Molecular Cardiology, University of Cincinnati, Ohio 45267, USA
    J Biol Chem 273:1511-8. 1998
    ..This is the first report demonstrating a role for MEF2 factors in smooth muscle-specific gene expression...
  19. ncbi Retinoic acid inhibits cardiac neural crest migration by blocking c-Jun N-terminal kinase activation
    J Li
    Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    Dev Biol 232:351-61. 2001
    ..These data demonstrate that the JNK signaling pathway and c-Jun activation are critical for cardiac neural crest outgrowth and are potential targets for the action of RA...
  20. ncbi The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice
    O F Bueno
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    EMBO J 19:6341-50. 2000
    ..The results of the present study indicate that the MEK1-ERK1/2 signaling pathway stimulates a physiologic hypertrophy response associated with augmented cardiac function and partial resistance to apoptotsis...
  21. ncbi Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses
    C Blanchard
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Mucosal Immunol 1:289-96. 2008
    ....
  22. ncbi Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability
    Toru Oka
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Ohio 45229 3039, USA
    Circ Res 98:837-45. 2006
    ..Thus, GATA4 is a necessary regulator of cardiac gene expression, hypertrophy, stress-compensation, and myocyte viability...
  23. ncbi Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents
    Xu Wu
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Clin Invest 119:976-85. 2009
    ..Thus, Pmca4b likely reduces the local Ca2+ signals involved in reactive cardiomyocyte hypertrophy via calcineurin regulation...
  24. ncbi Regulation of cardiac hypertrophy by intracellular signalling pathways
    Joerg Heineke
    Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
    Nat Rev Mol Cell Biol 7:589-600. 2006
    ..Recent findings in genetically modified animal models implicate important intermediate signal-transduction pathways in the coordination of heart growth following physiological and pathological stimulation...
  25. ncbi Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling
    Toru Oka
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Circ Res 101:313-21. 2007
    ..These are the first genetic data detailing the function of Pn in the adult heart as a regulator of cardiac remodeling and hypertrophy...
  26. ncbi Cdc42 is an antihypertrophic molecular switch in the mouse heart
    Marjorie Maillet
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, University of Cincinnati, and Experimental Hematology and Cancer Biology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    J Clin Invest 119:3079-88. 2009
    ....
  27. ncbi alpha1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice
    Hiroyuki Nakayama
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    J Clin Invest 119:3787-96. 2009
    ..Thus, cardiac alpha1G reexpression and its associated pool of T-type Ca2+ antagonize cardiac hypertrophy through a NOS3-dependent signaling mechanism...
  28. ncbi The transcription factor GATA-6 regulates pathological cardiac hypertrophy
    Jop H van Berlo
    Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229 3039, USA
    Circ Res 107:1032-40. 2010
    ..The highly related transcription factor GATA-6 is also expressed in the adult heart, although its role in controlling the hypertrophic program is unknown...
  29. ncbi TRPC channels are necessary mediators of pathologic cardiac hypertrophy
    Xu Wu
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 107:7000-5. 2010
    ..Thus, TRPC channels are necessary mediators of pathologic cardiac hypertrophy, in part through a calcineurin-NFAT signaling pathway...
  30. ncbi ASK1 regulates cardiomyocyte death but not hypertrophy in transgenic mice
    Qinghang Liu
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Circ Res 105:1110-7. 2009
    ..Apoptosis signal-regulating kinase (ASK)1 is a central upstream kinase in the greater mitogen-activated protein kinase cascade that mediates growth and death decisions in cardiac myocytes in response to diverse pathological stimuli...
  31. ncbi The IP3 receptor regulates cardiac hypertrophy in response to select stimuli
    Hiroyuki Nakayama
    Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229 3039, USA
    Circ Res 107:659-66. 2010
    ..Many prohypertrophic G protein-coupled receptor (GPCR) signaling events lead to IP(3) liberation, although its importance in transducing the hypertrophic response has not been established in vivo...
  32. ncbi The presence of Lys27 instead of Asn27 in human phospholamban promotes sarcoplasmic reticulum Ca2+-ATPase superinhibition and cardiac remodeling
    Wen Zhao
    Department of Pharmacology, University of Cincinnati College of Medicine, Cincinnati, OH 45267 0575, USA
    Circulation 113:995-1004. 2006
    ..The amino acid sequence of PLN is highly conserved, and although all species contain asparagine (Asn), human PLN is unique in containing lysine (Lys) at amino acid 27...
  33. ncbi Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure
    Hiroyuki Nakayama
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
    J Clin Invest 117:2431-44. 2007
    ....
  34. ncbi Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome
    Tomoki Nakamura
    Cincinnati Children s Hospital Medical Center, The Children s Hospital Research Foundation, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio 45229 3039, USA
    J Clin Invest 117:2123-32. 2007
    ....
  35. ncbi Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart
    Hiroyuki Nakayama
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    FASEB J 20:1660-70. 2006
    ..Thus, enhanced store-operated Ca2+ entry in the heart can regulate calcineurin-NFAT signaling in vivo, which could secondarily impact the hypertrophic response and cardiomyopathy...
  36. ncbi Direct interaction and reciprocal regulation between ASK1 and calcineurin-NFAT control cardiomyocyte death and growth
    Qinghang Liu
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC7020, Cincinnati Ohio 45229 3039, USA
    Mol Cell Biol 26:3785-97. 2006
    ....
  37. ncbi GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation
    Jian Xu
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Ohio 45229 3039, USA
    Circ Res 98:342-50. 2006
    ..These results identify GDF15 as a novel autocrine/endocrine factor that antagonizes the hypertrophic response and loss of ventricular performance, possibly through a mechanism involving SMAD proteins...
  38. ncbi Myocyte enhancer factors 2A and 2C induce dilated cardiomyopathy in transgenic mice
    Jian Xu
    Departments of Pharmacology and Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Biol Chem 281:9152-62. 2006
    ....
  39. ncbi Dichotomy of Ca2+ in the heart: contraction versus intracellular signaling
    Jeffery D Molkentin
    Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Clin Invest 116:623-6. 2006
    ....
  40. ncbi Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo
    Nicole H Purcell
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 104:14074-9. 2007
    ..Thus, ERK1/2 signaling is not required for mediating physiologic or pathologic cardiac hypertrophy in vivo, although it does play a protective role in response to pathologic stimuli...
  41. ncbi Inducible and myocyte-specific inhibition of PKCalpha enhances cardiac contractility and protects against infarction-induced heart failure
    Michael Hambleton
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Am J Physiol Heart Circ Physiol 293:H3768-71. 2007
    ..Thus, myocyte autonomous inhibition of PKCalpha protects the adult heart from decompensation and dilated cardiomyopathy after infarction injury in association with a primary enhancement in contractility...
  42. ncbi Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart
    Joerg Heineke
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Clin Invest 117:3198-210. 2007
    ..To our knowledge, these results demonstrate [corrected] a previously unrecognized function for GATA4 as a regulator of cardiac angiogenesis through a nonhypoxic, load, and/or disease-responsive mechanism...
  43. ncbi Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure
    Joerg Heineke
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, USA
    Circulation 121:419-25. 2010
    ..Myostatin is a cytokine of the transforming growth factor-beta superfamily that is known to control muscle wasting...
  44. ncbi CIB1 is a regulator of pathological cardiac hypertrophy
    Joerg Heineke
    Howard Hughes Medical Institute, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
    Nat Med 16:872-9. 2010
    ..Thus, CIB1 functions as a previously undescribed regulator of cardiac hypertrophy through its ability to regulate the association of calcineurin with the sarcolemma and its activation...
  45. ncbi FoxO transcription factors promote autophagy in cardiomyocytes
    Arunima Sengupta
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Medical Center, Cincinnati, Ohio 45229, USA
    J Biol Chem 284:28319-31. 2009
    ..Together these results provide evidence for an important role for FoxO1 and FoxO3 in regulating autophagy and cell size in cardiomyocytes...
  46. ncbi Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach
    Qinghang Liu
    Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, University of Cincinnati, Cincinnati, OH 45229 3039, USA
    Circ Res 105:194-200. 2009
    ....
  47. ncbi Cardiac myosin binding protein-C phosphorylation in a {beta}-myosin heavy chain background
    Sakthivel Sadayappan
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Ohio, USA
    Circulation 119:1253-62. 2009
    ..We determined the effect(s) of cMyBP-C phosphorylation in a beta-MyHC transgenic mouse heart in which >80% of the alpha-MyHC was replaced by beta-MyHC, which is the predominant myosin isoform in human cardiac muscle...
  48. ncbi Interaction between TAK1-TAB1-TAB2 and RCAN1-calcineurin defines a signalling nodal control point
    Qinghang Liu
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, and the Howard Hughes Medical Institute, Cincinnati, Ohio 45229, USA
    Nat Cell Biol 11:154-61. 2009
    ....
  49. ncbi Genetic manipulation of periostin expression in the heart does not affect myocyte content, cell cycle activity, or cardiac repair
    Angela Lorts
    Department of Pediatrics, Division of Cardiology, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Ohio, USA
    Circ Res 104:e1-7. 2009
    ..Periostin is a regulator of cardiac remodeling and hypertrophy and may be a reasonable pharmacological target to mitigate heart failure, but manipulation of this protein appears to have no obvious effect on myocardial regeneration...
  50. ncbi With great power comes great responsibility: using mouse genetics to study cardiac hypertrophy and failure
    Jeffery D Molkentin
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, OH, USA
    J Mol Cell Cardiol 46:130-6. 2009
    ....
  51. ncbi DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility
    Marjorie Maillet
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 283:31246-55. 2008
    ..These results demonstrate that ERK1/2 signaling is physiologically restrained by DUSP6 in coordinating cellular development and survival characteristics, directly impacting disease-responsiveness in adulthood...
  52. ncbi Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice
    John W Elrod
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Howard Hughes Medical Institute, Cincinnati, Ohio 45229, USA
    J Clin Invest 120:3680-7. 2010
    ..These findings suggest that the MPTP maintains homeostatic mitochondrial Ca(2+) levels to match metabolism with alterations in myocardial workload, thereby suggesting a physiologic function for the MPTP...
  53. ncbi Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in cardiac hypertrophy
    Izhak Kehat
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, and the Howard Hughes Medical Institute, Cincinnati, Ohio 45229 3039, USA
    Ann N Y Acad Sci 1188:96-102. 2010
    ..Thus, ERK1/2 signaling is not to be absolutely necessary for mediating cardiac hypertrophy, although it does appear to provide critical protective effects/signals during stress-stimulation...
  54. ncbi STRESS signaling pathways that modulate cardiac myocyte apoptosis
    Christopher P Baines
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
    J Mol Cell Cardiol 38:47-62. 2005
    ....
  55. ncbi Calcium-calcineurin signaling in the regulation of cardiac hypertrophy
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Biochem Biophys Res Commun 322:1178-91. 2004
    ..Finally, we will discuss emerging theories as to the mechanisms whereby alterations in intracellular calcium handling might stimulate calcineurin within the context of a contractile cell continually experiencing calcium flux...
  56. ncbi Calcineurin-NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs
    Jeffery D Molkentin
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Cardiovasc Res 63:467-75. 2004
    ..Thus, an emerging paradigm suggests that calcineurin-NFAT and MAPK signaling pathways are inter-dependent and together orchestrate the cardiac hypertrophic response...
  57. ncbi PKC-alpha regulates cardiac contractility and propensity toward heart failure
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Nat Med 10:248-54. 2004
    ..Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure...
  58. ncbi Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes
    Nicole H Purcell
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 24:1081-95. 2004
    ..Collectively, these results suggest that FHL2 serves a repressor function in cardiomyocytes through its ability to inhibit ERK1/2 transcriptional coupling...
  59. ncbi Calcineurin and cardiac hypertrophy: where have we been? Where are we going?
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, OH, USA
    J Physiol 541:1-8. 2002
    ..Finally, we will present evidence suggesting that calcineurin, as a Ca(2+)-responsive enzyme, may function as an internal load sensor in cardiac myocytes, matching output demands to hypertrophic growth...
  60. ncbi Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, Ohio 45229 3039, USA
    Circ Res 94:110-8. 2004
    ....
  61. ncbi Involvement of extracellular signal-regulated kinases 1/2 in cardiac hypertrophy and cell death
    Orlando F Bueno
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA
    Circ Res 91:776-81. 2002
    ....
  62. ncbi Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy between cultured myocytes and animal models
    Qiangrong Liang
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA
    J Mol Cell Cardiol 35:1385-94. 2003
    ..However, SAPK signaling is likely maladaptive, despite its putative anti-hypertrophic role in vivo, given the observation of dilated cardiomyopathy and heart failure in gain-of-function transgenic models...
  63. ncbi NFATc3 and NFATc4 are required for cardiac development and mitochondrial function
    Paul B Bushdid
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center Cincinnati, ML 7020, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
    Circ Res 92:1305-13. 2003
    ..Together, these data support the hypothesis that loss of NFAT activity in the heart results in a deficiency in mitochondrial energy metabolism required for cardiac morphogenesis and function...
  64. ncbi Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction
    Orlando F Bueno
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Circ Res 94:91-9. 2004
    ..These results represent the first genetic loss-of-function data showing a prosurvival role for calcineurin-NFAT signaling in the heart...
  65. ncbi Cardiac function and electrical remodeling of the calcineurin-overexpressed transgenic mouse
    Natalia N Petrashevskaya
    Institute of Molecular Pharmacology and Biophysics, Department of Surgery, Cardiovascular Research Center, University of Cincinnati, 231 Albert Sabin Way, OH 45267, USA
    Cardiovasc Res 54:117-32. 2002
    ..This type of functional hypertrophic remodeling is accompanied by a negative feedback regulation between increased calcium handling and beta-adrenergic contractile activation...
  66. ncbi Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    J Clin Invest 111:1475-86. 2003
    ..Collectively, these observations indicate that reduced p38 signaling in the heart promotes myocyte growth through a mechanism involving enhanced calcineurin-NFAT signaling...
  67. ncbi The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment
    Yan Shan Dai
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, MLC7020, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 25:9936-48. 2005
    ..Collectively, our results define a novel response pathway whereby NFATc3 is negatively regulated by class II histone deacetylases through the DnaJ (heat shock protein-40) superfamily member Mrj...
  68. ncbi Regulation of calcineurin through transcriptional induction of the calcineurin A beta promoter in vitro and in vivo
    Toru Oka
    Cincinnati Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, MLC7020, Cincinnati OH 45229 3039, USA
    Mol Cell Biol 25:6649-59. 2005
    ....
  69. ncbi Adenine nucleotide translocase-1 induces cardiomyocyte death through upregulation of the pro-apoptotic protein Bax
    Christopher P Baines
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Mol Cell Cardiol 46:969-77. 2009
    ..Taken together, these data indicate that ANT mediates cell death, not through the MPT pore, but rather via a ROS-dependent upregulation and activation of Bax...
  70. ncbi Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death
    Christopher P Baines
    Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    Nature 434:658-62. 2005
    ..Thus, cyclophilin D and the mitochondrial permeability transition are required for mediating Ca2+- and oxidative damage-induced cell death, but not Bcl-2 family member-regulated death...
  71. ncbi Impaired cardiac hypertrophic response in Calcineurin Abeta -deficient mice
    Orlando F Bueno
    Divisions of Molecular Cardiovascular Biology and Cardiology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 99:4586-91. 2002
    ..Collectively, these data solidify the hypothesis that calcineurin functions as a central regulator of the cardiac hypertrophic growth response in vivo...
  72. ncbi Calcineurin and hypertrophic heart disease: novel insights and remaining questions
    Orlando F Bueno
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati OH, USA
    Cardiovasc Res 53:806-21. 2002
    ....
  73. ncbi Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth
    Bastiano Sanna
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC7020, Cincinnati, OH 45229 3039, USA
    Mol Cell Biol 25:865-78. 2005
    ..Collectively, these results indicate that calcineurin-NFAT and MEK1-ERK1/2 pathways constitute a codependent signaling module in cardiomyocytes that coordinately regulates the growth response through two distinct mechanisms...
  74. ncbi The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism
    Yan Shan Dai
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 277:24390-8. 2002
    ....
  75. ncbi Reduction of I(to) causes hypertrophy in neonatal rat ventricular myocytes
    Zamaneh Kassiri
    Department of Physiology, Heart and Stroke/Richard Lewar Center, University of Toronto, Toronto, Canada
    Circ Res 90:578-85. 2002
    ..2)N infection were prevented by blocking Ca2+ entry and excitability with verapamil or high [K+]o. Our studies suggest that reductions of K(v4.2/3)-based I(to) play a role in hypertrophy signaling by activation of calcineurin...
  76. ncbi Calcineurin transgenic mice have mitochondrial dysfunction and elevated superoxide production
    M R Sayen
    The Scripps Research Institute, La Jolla, California 92037, USA
    Am J Physiol Cell Physiol 284:C562-70. 2003
    ..Taken together, these data indicate that calcineurin signaling affects mitochondrial energetics and superoxide production. The excessive production of superoxide may contribute to the development of cardiac failure...
  77. ncbi Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart
    Paige Snider
    Cardiovascular Development Group, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA
    Circ Res 102:752-60. 2008
    ..Thus, peri(lacZ) knockouts provide a new model of viable latent valve disease...
  78. ncbi Temporal activation of c-Jun N-terminal kinase in adult transgenic heart via cre-loxP-mediated DNA recombination
    Brian G Petrich
    Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA
    FASEB J 17:749-51. 2003
    ..Our data also demonstrated that the inducible gene-switch approach reported here may also be applicable in other studies to achieve efficient, tissue-specific, and temporally regulated genetic manipulation in intact animals...
  79. ncbi Calreticulin signals upstream of calcineurin and MEF2C in a critical Ca(2+)-dependent signaling cascade
    Jeffrey Lynch
    Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    J Cell Biol 170:37-47. 2005
    ..Our study illustrates the existence of a positive feedback mechanism that ensures an adequate supply of releasable Ca(2+) is maintained within the cell for activation of calcineurin and, subsequently, for proper functioning of MEF2C...
  80. ncbi Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes
    Beate Fiedler
    Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
    Proc Natl Acad Sci U S A 99:11363-8. 2002
    ..Inhibition of calcineurin-NFAT signaling by PKG I provides a framework for understanding how NO inhibits cardiac myocyte hypertrophy...
  81. ncbi Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy
    Eva van Rooij
    Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital, P Debyelaan 25, The Netherlands
    J Biol Chem 277:48617-26. 2002
    ..These results indicate that multiple NFAT isoforms are expressed in cardiomyocytes where they function as necessary transducers of calcineurin in facilitating cardiomyocyte hypertrophy...
  82. ncbi Divergent signaling pathways converge on GATA4 to regulate cardiac hypertrophic gene expression
    Qiangrong Liang
    J Mol Cell Cardiol 34:611-6. 2002
  83. ncbi Requirement of transcription factor NFAT in developing atrial myocardium
    William Schubert
    Dept of Molecular Pharmacology, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, NY 10461, USA
    J Cell Biol 161:861-74. 2003
    ..Thus, regulation of cytoskeletal protein gene expression by NFAT may be important for the structural architecture of the developing atrial myocardium...
  84. ncbi Is nuclear factor kappaB an attractive therapeutic target for treating cardiac hypertrophy?
    Nicole H Purcell
    Circulation 108:638-40. 2003
  85. ncbi Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure
    Igor Kostetskii
    Center for Research on Reproduction and Women s Health, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Circ Res 96:346-54. 2005
    ....
  86. ncbi The beta-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy
    Xin Chen
    Molecular Cardiology Research Institute, Tufts New England Medical Center and Tufts University School of Medicine, USA
    Mol Cell Biol 26:4462-73. 2006
    ..Thus, our studies, employing complementary models in vivo, implicate beta-catenin/Tcf/Lef signaling as an essential growth-regulatory pathway in terminally differentiated cells...
  87. ncbi Calcineurin regulates NFAT-dependent iNOS expression and protection of cardiomyocytes: co-operation with Src tyrosine kinase
    Kofo Obasanjo-Blackshire
    Cardiovascular Division, King's College London School of Medicine, Department of Cardiology, The Rayne Institute, St Thomas's Hospital, Lambeth Palace Road, London SE1 7EH, UK
    Cardiovasc Res 71:672-83. 2006
    ..CONCLUSIONS: These results support a cardioprotective role for calcineurin mediated by NFAT-dependent induction of iNOS expression and co-operativity between calcineurin and Src...
  88. ncbi Locating heart failure
    Jeffery D Molkentin
    Nat Med 11:1284-5. 2005
  89. ncbi Inducible cardiac-restricted expression of enteroviral protease 2A is sufficient to induce dilated cardiomyopathy
    Dingding Xiong
    University of California, San Diego, Department of Medicine, 9500 Gilman Dr, La Jolla, CA 92093, USA
    Circulation 115:94-102. 2007
    ..However, the direct effect of protease 2A in enteroviral cardiomyopathy is less clear because other viral proteins are also expressed with viral infection...
  90. ncbi Cardiac hypertrophy and reduced contractility in hearts deficient in the titin kinase region
    Jun Peng
    Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164 6520, USA
    Circulation 115:743-51. 2007
    ..We developed a knockout in which expression of M-line-deficient titin can be induced in adult mice and investigated the role of the titin kinase region in cardiac function...
  91. ncbi Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle
    Katsuhisa Matsuura
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
    J Cell Biol 167:351-63. 2004
    ..These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes...
  92. ncbi Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury
    Patrick C H Hsieh
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA
    Nat Med 13:970-4. 2007
    ..5% in areas bordering a myocardial infarction, 76.6% in areas away from a myocardial infarction, and 75.7% in hearts subjected to pressure overload, indicating that stem cells or precursor cells had refreshed the cardiomyocytes...
  93. ncbi Glycogen synthase kinase-3beta regulates growth, calcium homeostasis, and diastolic function in the heart
    Ashour Michael
    Boston University Medical Center and School of Medicine, Boston, MA 02118, USA
    J Biol Chem 279:21383-93. 2004
    ..Because down-regulation of SERCA2a plays a central role in the diastolic and systolic dysfunction of patients with heart failure, these findings have potential implications for the therapy of this disorder...
  94. ncbi Calcineurin-induced energy wasting in a transgenic mouse model of heart failure
    Ilka Pinz
    NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Am J Physiol Heart Circ Physiol 294:H1459-66. 2008
    ....
  95. ncbi Nuclear Dbf2-related protein kinases (NDRs) in isolated cardiac myocytes and the myocardium: activation by cellular stresses and by phosphoprotein serine-/threonine-phosphatase inhibitors
    Stephen J Fuller
    National Heart and Lung Institute NHLI Division, Faculty of Medicine, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK
    Cell Signal 20:1564-77. 2008
    ..From a pathological viewpoint, we conclude that activities of NDR1 and NDR2 are responsive to cytotoxic stresses in heart preparations and this may represent a previously-unidentified response to myocardial ischaemia in vivo...
  96. ncbi A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy
    Tetsuro Ago
    Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
    Cell 133:978-93. 2008
    ..Our study reveals a novel regulatory mechanism of cardiac hypertrophy through which the nucleocytoplasmic shuttling of class II HDACs is modulated by their redox modification in a Trx1-sensitive manner...
  97. ncbi Does contractile Ca2+ control calcineurin-NFAT signaling and pathological hypertrophy in cardiac myocytes?
    Steven R Houser
    Department of Physiology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA
    Sci Signal 1:pe31. 2008
    ..Here, we critically review evidence that supports the hypothesis that calcineurin-NFAT signaling is regulated by contractile Ca(2+) transients in cardiac myocytes...
  98. ncbi Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling
    Paula A da Costa Martins
    Department of Medical Physiology, University Medical Center Utrecht, Utrecht, Netherlands
    Circulation 118:1567-76. 2008
    ..Dicer, an RNAse III endonuclease critical for processing of pre-microRNAs (miRNAs) into mature 22-nucleotide miRNAs, has proven a useful target to dissect the significance of miRNAs biogenesis in mammalian biology...
  99. ncbi Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis
    Jifen Li
    Center for Research on Reproduction and Women s Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Circ Res 97:474-81. 2005
    ..Our data suggest that perturbation of the N-cadherin/catenin complex in heart disease may be an underlying cause, leading to the establishment of the arrythmogenic substrate by destabilizing gap junctions at the cell surface...