Stephan E Lehnart

Summary

Affiliation: Columbia University
Country: USA

Publications

  1. pmc Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency
    Mark A Oyama
    University of Pennsylvania, Philadelphia, PA, USA, USA
    J Vet Cardiol 10:1-10. 2008
  2. ncbi request reprint Modulation of the ryanodine receptor and intracellular calcium
    Ran Zalk
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Annu Rev Biochem 76:367-85. 2007
  3. ncbi request reprint Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affe
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, P and S 9 401 box 22, 630 W 168 St, New York, NY 10032, USA
    Circulation 116:2325-45. 2007
  4. ncbi request reprint Novel targets for treating heart and muscle disease: stabilizing ryanodine receptors and preventing intracellular calcium leak
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Curr Opin Pharmacol 7:225-32. 2007
  5. ncbi request reprint Calstabin deficiency, ryanodine receptors, and sudden cardiac death
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, 630W 168th Street, P and S 9 401, New York, NY 10032, USA
    Biochem Biophys Res Commun 322:1267-79. 2004
  6. pmc Stabilization of cardiac ryanodine receptor prevents intracellular calcium leak and arrhythmias
    Stephan E Lehnart
    Department of Physiology, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:7906-10. 2006
  7. pmc Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias
    Stephan E Lehnart
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell 123:25-35. 2005
  8. ncbi request reprint Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak
    Stephan E Lehnart
    Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 W 168th St, P and S 9 401, Box 65, New York, NY 10032, USA
    Circulation 109:3208-14. 2004
  9. pmc Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:9607-12. 2005
  10. pmc Phosphorylation of the ryanodine receptor mediates the cardiac fight or flight response in mice
    Jian Shan
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    J Clin Invest 120:4388-98. 2010

Detail Information

Publications27

  1. pmc Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency
    Mark A Oyama
    University of Pennsylvania, Philadelphia, PA, USA, USA
    J Vet Cardiol 10:1-10. 2008
    ..To examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC)...
  2. ncbi request reprint Modulation of the ryanodine receptor and intracellular calcium
    Ran Zalk
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Annu Rev Biochem 76:367-85. 2007
    ..This review focuses on recent progress in the understanding of RyR regulation and disease mechanisms that are associated with channel dysfunction...
  3. ncbi request reprint Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affe
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, P and S 9 401 box 22, 630 W 168 St, New York, NY 10032, USA
    Circulation 116:2325-45. 2007
    ....
  4. ncbi request reprint Novel targets for treating heart and muscle disease: stabilizing ryanodine receptors and preventing intracellular calcium leak
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Curr Opin Pharmacol 7:225-32. 2007
    ..Recently, the efficacy of novel Ca(2+) release channel-stabilizing drugs has been demonstrated in cardiac and skeletal muscle disease models...
  5. ncbi request reprint Calstabin deficiency, ryanodine receptors, and sudden cardiac death
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, 630W 168th Street, P and S 9 401, New York, NY 10032, USA
    Biochem Biophys Res Commun 322:1267-79. 2004
    ....
  6. pmc Stabilization of cardiac ryanodine receptor prevents intracellular calcium leak and arrhythmias
    Stephan E Lehnart
    Department of Physiology, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:7906-10. 2006
    ..Our data suggest that calstabin-2 deficiency is as a critical mediator of triggers that initiate cardiac arrhythmias...
  7. pmc Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias
    Stephan E Lehnart
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
    Cell 123:25-35. 2005
    ..These data suggest that reduced PDE4D activity causes defective RyR2-channel function associated with heart failure and arrhythmias...
  8. ncbi request reprint Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak
    Stephan E Lehnart
    Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 W 168th St, P and S 9 401, Box 65, New York, NY 10032, USA
    Circulation 109:3208-14. 2004
    ....
  9. pmc Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:9607-12. 2005
    ..We conclude that JTV519 may provide a specific way to treat the cardiac and skeletal muscle myopathy in HF by increasing calstabin binding to RyR...
  10. pmc Phosphorylation of the ryanodine receptor mediates the cardiac fight or flight response in mice
    Jian Shan
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    J Clin Invest 120:4388-98. 2010
    ..These studies identify what we believe to be new roles for PKA phosphorylation of RyR2 in both the heart rate and contractile responses to acute catecholaminergic stimulation...
  11. ncbi request reprint Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Science 304:292-6. 2004
    ..Thus, enhancing the binding of calstabin2 to RyR2 may be a therapeutic strategy for common ventricular arrhythmias...
  12. ncbi request reprint Defective cardiac ryanodine receptor regulation during atrial fibrillation
    John A Vest
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Circulation 111:2025-32. 2005
    ..6) causes SR Ca2+ leak in failing hearts and can trigger fatal ventricular arrhythmias. Little is known about the role of RyR2 dysfunction in AF, however...
  13. ncbi request reprint FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Cell 113:829-40. 2003
    ..6 for RyR2 and increased single-channel activity under conditions that simulate exercise. These data suggest that "leaky" RyR2 channels can trigger fatal cardiac arrhythmias, providing a possible explanation for CPVT...
  14. pmc Ryanodine receptor/calcium release channel PKA phosphorylation: a critical mediator of heart failure progression
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:511-8. 2006
    ..Taken together, these data show that PKA phosphorylation of Ser-2808 on the RyR2 channel appears to be a critical mediator of progressive cardiac dysfunction after myocardial infarction...
  15. ncbi request reprint Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 W 168th St, P and S 9 401, Box 65, New York, NY 10032, USA
    Circ Res 94:e61-70. 2004
    ..CaMKII-mediated phosphorylation of RyR2 may contribute to the enhanced contractility observed at higher heart rates. The full text of this article is available online at http://circres.ahajournals.org...
  16. pmc Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity
    Andrew M Bellinger
    Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 105:2198-202. 2008
    ..Taken together, these data suggest a possible mechanism by which Ca2+ leak via calstabin1-depleted RyR1 channels leads to defective Ca2+ signaling, muscle damage, and impaired exercise capacity...
  17. pmc Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 118:2230-45. 2008
    ..Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death...
  18. ncbi request reprint Immunophilins and coupled gating of ryanodine receptors
    Stephan E Lehnart
    Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, N Y 10032, USA
    Curr Top Med Chem 3:1383-91. 2003
    ....
  19. ncbi request reprint Ryanodine receptor-targeted anti-arrhythmic therapy
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Ann N Y Acad Sci 1047:366-75. 2005
    ....
  20. ncbi request reprint Intracellular calcium release and cardiac disease
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA
    Annu Rev Physiol 67:69-98. 2005
    ..The chronically activated fight or flight response leads to leaky channels, altered calcium signaling, and contractile dysfunction and cardiac arrhythmias...
  21. ncbi request reprint Cardiac ryanodine receptor function and regulation in heart disease
    Stephan E Lehnart
    Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
    Ann N Y Acad Sci 1015:144-59. 2004
    ..In conclusion, heart failure and exercise-induced sudden cardiac death have been linked to defects in RyR2-calstabin2 regulation, and this may represent a novel target for the prevention and treatment of these forms of heart disease...
  22. pmc Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins
    Antoine Muchir
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    Hum Mol Genet 18:241-7. 2009
    ..They further provide proof of principle for ERK inhibition as a therapeutic option to prevent or delay heart failure in humans with Emery-Dreifuss muscular dystrophy and related disorders caused by mutations in LMNA...
  23. ncbi request reprint Phosphodiesterase 4D and heart failure: a cautionary tale
    Stephan E Lehnart
    Columbia University, Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, New York, NY 10032, USA
    Expert Opin Ther Targets 10:677-88. 2006
    ..The authors review the contribution of PDE activity in the heart to contractile stress adaptation, the significance of altered cAMP signalling in heart failure, and the effects of PDE inhibition in heart disease...
  24. pmc PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure
    Steven Reiken
    Center for Molecular Cardiology, Box 65, Columbia University College of Physicians and Surgeons, Room 9 401, 630 West 168th Street, New York, NY 10032, USA
    J Cell Biol 160:919-28. 2003
    ..PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF...
  25. ncbi request reprint Defective ryanodine receptor interdomain interactions may contribute to intracellular Ca2+ leak: a novel therapeutic target in heart failure
    Stephan E Lehnart
    Circulation 111:3342-6. 2005
  26. ncbi request reprint Intracellular beta-blockade: overexpression of Galpha(i2) depresses the beta-adrenergic response in intact myocardium
    Paul M L Janssen
    Department Cardiology and Pneumology, University of Gottingen, Gottingen, Germany
    Cardiovasc Res 55:300-8. 2002
    ..Increased levels of inhibitory G proteins have been observed in heart failure, but their physiological relevance in mediating the reduced beta-adrenergic response is largely unknown...
  27. ncbi request reprint Potentiation of beta-adrenergic inotropic response by pyruvate in failing human myocardium
    Hans Peter Hermann
    Abteilung Kardiologie und Pneumologie, Georg August Universitat Gottingen, Robert Koch Str 40, D 37075 Gottingen, Germany
    Cardiovasc Res 53:116-23. 2002
    ....