Jeffrey Saffitz

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. doi request reprint The pathobiology of arrhythmogenic cardiomyopathy
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Annu Rev Pathol 6:299-321. 2011
  2. doi request reprint Arrhythmogenic right ventricular cardiomyopathy: new insights into disease mechanisms and diagnosis
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    J Investig Med 57:861-4. 2009
  3. doi request reprint Arrhythmogenic cardiomyopathy and abnormalities of cell-to-cell coupling
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Heart Rhythm 6:S62-5. 2009
  4. ncbi request reprint Remodeling of gap junctions in ischemic and nonischemic forms of heart disease
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    J Membr Biol 218:65-71. 2007
  5. ncbi request reprint Adhesion molecules: why they are important to the electrophysiologist
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Cardiovasc Electrophysiol 17:225-9. 2006
  6. ncbi request reprint Douglas P. Zipes Lecture. Biology and pathobiology of cardiac connexins: from cell to bedside
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Heart Rhythm 3:102-7. 2006
  7. doi request reprint Metastatic peritoneal mesothelioma in the setting of recurrent ascites: a case report
    Von Samedi
    Department of Pathology, Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts 02215 5400, USA
    Diagn Cytopathol 38:675-81. 2010
  8. ncbi request reprint Dependence of electrical coupling on mechanical coupling in cardiac myocytes: insights gained from cardiomyopathies caused by defects in cell-cell connections
    Jeffrey E Saffitz
    Department of Pathology, Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Ann N Y Acad Sci 1047:336-44. 2005
  9. doi request reprint A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy
    Angeliki Asimaki
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    N Engl J Med 360:1075-84. 2009
  10. ncbi request reprint Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy
    Joseph J Gard
    Department of Pathology, Box 8118, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Cardiovasc Res 67:539-47. 2005

Research Grants

  1. Disease Mechanisms in ARVC
    Jeffrey E Saffitz; Fiscal Year: 2010
  2. REGULATION OF MYOCARDIAL GAP JUNCTIONS
    Jeffrey Saffitz; Fiscal Year: 2002
  3. REGULATION OF MYOCARDIAL GAP JUNCTIONS
    Jeffrey Saffitz; Fiscal Year: 2005
  4. REGULATION OF MYOCARDIAL GAP JUNCTIONS
    Jeffrey Saffitz; Fiscal Year: 2006
  5. CX43 IN A GENETIC MODEL OF ALTERED MYOCARDIAL CONDUCTION
    Jeffrey Saffitz; Fiscal Year: 2004
  6. CX43 IN A GENETIC MODEL OF ALTERED MYOCARDIAL CONDUCTION
    Jeffrey Saffitz; Fiscal Year: 2000

Collaborators

Detail Information

Publications39

  1. doi request reprint The pathobiology of arrhythmogenic cardiomyopathy
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Annu Rev Pathol 6:299-321. 2011
    ....
  2. doi request reprint Arrhythmogenic right ventricular cardiomyopathy: new insights into disease mechanisms and diagnosis
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    J Investig Med 57:861-4. 2009
    ..This review highlights recent advances in understanding the pathogenesis of ARVC and presents evidence, suggesting that the disease is caused by a combination of altered cellular biomechanical behavior and altered signaling...
  3. doi request reprint Arrhythmogenic cardiomyopathy and abnormalities of cell-to-cell coupling
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Heart Rhythm 6:S62-5. 2009
    ....
  4. ncbi request reprint Remodeling of gap junctions in ischemic and nonischemic forms of heart disease
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    J Membr Biol 218:65-71. 2007
    ..This review is focused on selected aspects of this work pertaining to changes in coupling in response to acute and chronic ischemic heart disease and in familial cardiomyopathies caused by mutations in genes encoding desmosomal proteins...
  5. ncbi request reprint Adhesion molecules: why they are important to the electrophysiologist
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Cardiovasc Electrophysiol 17:225-9. 2006
  6. ncbi request reprint Douglas P. Zipes Lecture. Biology and pathobiology of cardiac connexins: from cell to bedside
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Heart Rhythm 3:102-7. 2006
    ..It highlights recent advances and new research directions in gap junction biology...
  7. doi request reprint Metastatic peritoneal mesothelioma in the setting of recurrent ascites: a case report
    Von Samedi
    Department of Pathology, Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts 02215 5400, USA
    Diagn Cytopathol 38:675-81. 2010
    ....
  8. ncbi request reprint Dependence of electrical coupling on mechanical coupling in cardiac myocytes: insights gained from cardiomyopathies caused by defects in cell-cell connections
    Jeffrey E Saffitz
    Department of Pathology, Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Ann N Y Acad Sci 1047:336-44. 2005
    ..This could contribute to the high incidence of ventricular arrhythmias and sudden death known to occur in these cardiomyopathies...
  9. doi request reprint A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy
    Angeliki Asimaki
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    N Engl J Med 360:1075-84. 2009
    ..The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) can be challenging because the clinical presentation is highly variable and genetic penetrance is often low...
  10. ncbi request reprint Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy
    Joseph J Gard
    Department of Pathology, Box 8118, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Cardiovasc Res 67:539-47. 2005
    ....
  11. ncbi request reprint Distinct pathways regulate expression of cardiac electrical and mechanical junction proteins in response to stretch
    Kiyomi Yamada
    Department of Pathology, Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO, USA
    Circ Res 97:346-53. 2005
    ..In contrast, stretch-induced upregulation of adhesion junction proteins involves intracellular mechanotransduction pathways initiated via integrin signaling and acting downstream of src kinase...
  12. doi request reprint Arrhythmogenic right ventricular cardiomyopathy: new insights into mechanisms of disease
    Jeffrey E Saffitz
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    Cardiovasc Pathol 19:166-70. 2010
    ....
  13. ncbi request reprint The pathology of sudden cardiac death in patients with ischemic heart disease--arrhythmology for anatomic pathologists
    Jeffrey E Saffitz
    Department of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cardiovasc Pathol 14:195-203. 2005
    ..A basic knowledge of arrhythmia mechanisms is necessary to understand the role of pathologic anatomy in the pathophysiology of sudden death...
  14. ncbi request reprint Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts
    Michael A Laflamme
    Department of Pathology, University of Washington, Seattle, Washington, USA
    Circ Res 90:634-40. 2002
    ..quot; Thus, adult humans have extracardiac progenitor cells capable of migrating to and repopulating damaged myocardium, but this process occurs at very low levels...
  15. ncbi request reprint Mechanisms of delayed electrical uncoupling induced by ischemic preconditioning
    Sandeep K Jain
    Department of Medicine, Washington University, St Louis, MO 63110, USA
    Circ Res 92:1138-44. 2003
    ..Both of these effects are regulated by activation of KATP channels, whereas PKC plays a role in internalization of Cx43...
  16. ncbi request reprint Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy
    Zhao Yang
    Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Circ Res 99:646-55. 2006
    ..These data suggest DSP expression in cardiomyocytes is crucial for maintaining cardiac tissue integrity, and DSP abnormalities result in ARVD/C by cardiomyocyte death, changes in lipid metabolism, and defects in cardiac development...
  17. ncbi request reprint Relative contributions of connexins 40 and 43 to atrial impulse propagation in synthetic strands of neonatal and fetal murine cardiomyocytes
    Philippe Beauchamp
    Department of Physiology, University of Bern, Switzerland
    Circ Res 99:1216-24. 2006
    ....
  18. ncbi request reprint c-Jun N-terminal kinase activation mediates downregulation of connexin43 in cardiomyocytes
    Brian G Petrich
    Department of Cell Biology, The Scripps Research Institute, La Jolla, Calif, USA
    Circ Res 91:640-7. 2002
    ..Our report represents the first evidence, both in vitro and in vivo, implicating JNK as an important mediator of stress-induced Cx43 downregulation and impaired intercellular communication in the failing heart...
  19. ncbi request reprint Targeted activation of c-Jun N-terminal kinase in vivo induces restrictive cardiomyopathy and conduction defects
    Brian G Petrich
    Departments of Anesthesiology and Medicine, UCLA, Los Angeles, California 90095, USA
    J Biol Chem 279:15330-8. 2004
    ..These results represent the first characterization of JNK-mediated cardiac pathology in vivo and support an important role for JNK signaling in specific aspects of cardiac remodeling in the pathogenesis of cardiac disease...
  20. ncbi request reprint Redistribution of connexin45 in gap junctions of connexin43-deficient hearts
    Carolyn M Johnson
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Cardiovasc Res 53:921-35. 2002
    ..The present study was undertaken to determine (1) whether expression of Cx45 is upregulated and (2) whether gap junction structure and distribution are altered in Cx43-deficient mice...
  21. ncbi request reprint Effects of mechanical forces and mediators of hypertrophy on remodeling of gap junctions in the heart
    Jeffrey E Saffitz
    Center for Cardiovascular Research and the Department of Pathology, University of Bern, Bern, Switzerland
    Circ Res 94:585-91. 2004
    ..The molecular mechanisms responsible for the interaction between mechanical and functional cell-to-cell coupling remain to be elucidated...
  22. ncbi request reprint Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease)
    Starr R Kaplan
    Department of Pathology and Center for Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri 63100, USA
    Heart Rhythm 1:3-11. 2004
    ....
  23. ncbi request reprint Electrical propagation in synthetic ventricular myocyte strands from germline connexin43 knockout mice
    Philippe Beauchamp
    Department of Physiology, University of Bern, Switzerland
    Circ Res 95:170-8. 2004
    ..In summary, knockout of Cx43 in ventricular myocytes leads to very slow conduction dependent on the presence of Cx45. Electrical field effect transmission does not contribute to propagation in synthetic strands...
  24. pmc Protein kinase Cepsilon mediates salutary effects on electrical coupling induced by ischemic preconditioning
    Thomas J Hund
    Department of Surgery, School of Medicine, Washington University, St Louis, Missouri, USA
    Heart Rhythm 4:1183-93. 2007
    ..Ischemic preconditioning delays the onset of electrical uncoupling and prevents loss of the primary ventricular gap junction protein connexin 43 (Cx43) from gap junctions during subsequent ischemia...
  25. pmc A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy
    Angeliki Asimaki
    Department of Medicine, The Heart Hospital, University College London Hospitals, London, National Health Service Trust, UK
    Am J Hum Genet 81:964-73. 2007
    ..These results implicate novel molecular mechanisms in the pathogenesis of ARVC...
  26. ncbi request reprint Transmural distribution of connexins in rodent hearts
    Kathryn A Yamada
    Department of Medicine Cardiovascular Division, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Cardiovasc Electrophysiol 15:710-5. 2004
    ..However, little is known about the transmural distribution of cardiac gap junction proteins...
  27. ncbi request reprint Autocrine regulation of myocyte Cx43 expression by VEGF
    Rhea C Pimentel
    Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
    Circ Res 90:671-7. 2002
    ..Because the cultures contained only approximately 5% nonmyocytic cells, these results indicate that myocyte-derived VEGF, secreted in response to stretch, acts in an autocrine fashion to enhance intercellular coupling...
  28. ncbi request reprint Spontaneous and inducible ventricular arrhythmias after myocardial infarction in mice
    Tetsuo Betsuyaku
    Department of Medicine Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA
    Cardiovasc Pathol 13:156-64. 2004
    ..We addressed this question using hearts from mice heterozygous for a connexin43 null allele (Cx43(+/-))...
  29. ncbi request reprint Connexin43 as a determinant of myocardial infarct size following coronary occlusion in mice
    Shigeto Kanno
    Department of Surgery, Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA
    J Am Coll Cardiol 41:681-6. 2003
    ..The purpose of this study was to define the role of cell-cell coupling as an independent determinant of infarct size following coronary occlusion...
  30. ncbi request reprint Mechanoelectrical feedback as novel mechanism of cardiac electrical remodeling
    Darwin Jeyaraj
    Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Dr, Cleveland, OH 44109 1998, USA
    Circulation 115:3145-55. 2007
    ..Although T-wave memory is associated with altered expression of sarcolemmal ion channels, the biophysical mechanisms responsible for triggering remodeling of cardiac ion channels are unknown...
  31. ncbi request reprint Diminished zonula occludens-1 expression in the failing human heart
    James G Laing
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Cardiovasc Pathol 16:159-64. 2007
    ..Here, we determined whether expression of ZO-1 is altered in patients with heart failure...
  32. ncbi request reprint Dramatic accumulation of triglycerides and precipitation of cardiac hemodynamic dysfunction during brief caloric restriction in transgenic myocardium expressing human calcium-independent phospholipase A2gamma
    David J Mancuso
    Division of Bioorganic Chemistry and Molecular Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 282:9216-27. 2007
    ....
  33. pmc Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis
    Atsushi Sanbe
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Children s Hospital Research Foundation, Mail Location Code 7020, 3333 Burnet Avenue, OH 45229 3039, USA
    Proc Natl Acad Sci U S A 101:10132-6. 2004
    ..These oligomeric amyloid intermediates are present also in cardiomyocytes derived from many human dilated and hypertrophic cardiomyopathies...
  34. ncbi request reprint Matrix-protein-specific regulation of Cx43 expression in cardiac myocytes subjected to mechanical load
    Amit J Shanker
    Department of Pathology and the Center for Cardiovascular Research, Washington University School of Medicine, St Louis, MO 63110, USA
    Circ Res 96:558-66. 2005
    ..Changes in the composition of the extracellular matrix may affect electrical coupling in cardiac myocytes...
  35. ncbi request reprint Connexins, conduction, and atrial fibrillation
    Jeffrey E Saffitz
    N Engl J Med 354:2712-4. 2006
  36. pmc Impulse propagation in synthetic strands of neonatal cardiac myocytes with genetically reduced levels of connexin43
    Stuart P Thomas
    Department of Physiology, University of Bern, Bühlplatz5, CH 3012 Bern, Switzerland
    Circ Res 92:1209-16. 2003
    ..The lack of changes in theta in this tissue is explained by the dominating role of myoplasmic resistance and the compensatory increase of dV/dtmax...
  37. ncbi request reprint Structural heart disease, SCN5A gene mutations, and Brugada syndrome: a complex ménage à trois
    Jeffrey E Saffitz
    Circulation 112:3672-4. 2005
  38. ncbi request reprint Extracardiac progenitor cells repopulate most major cell types in the transplanted human heart
    Elina Minami
    Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
    Circulation 112:2951-8. 2005
    ..Here, we explored the extent of endothelial, smooth muscle, and Schwann cell chimerism in patients with sex-mismatched (female-to-male) heart transplants...
  39. ncbi request reprint Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner
    Laurie K Russell
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Circ Res 94:525-33. 2004
    ....

Research Grants26

  1. Disease Mechanisms in ARVC
    Jeffrey E Saffitz; Fiscal Year: 2010
    ..Our ultimate goal is to help develop mechanism-based therapies to prevent sudden death. ..
  2. REGULATION OF MYOCARDIAL GAP JUNCTIONS
    Jeffrey Saffitz; Fiscal Year: 2002
    ..The results of the proposed research will provide new insights into fundamental mechanisms of arrhythmogenesis in heart failure. ..
  3. REGULATION OF MYOCARDIAL GAP JUNCTIONS
    Jeffrey Saffitz; Fiscal Year: 2005
    ..In this application, we request funds for acquisition of additional equipment and implementation of a maintenance program that will ensure continued availability .of confocal microscopy resources for our research. ..
  4. REGULATION OF MYOCARDIAL GAP JUNCTIONS
    Jeffrey Saffitz; Fiscal Year: 2006
    ..abstract_text> ..
  5. CX43 IN A GENETIC MODEL OF ALTERED MYOCARDIAL CONDUCTION
    Jeffrey Saffitz; Fiscal Year: 2004
    ..The results of the proposed research will define mechanisms by which reduced coupling promotes ventricular tachyarrhythmias in mouse models of acute and chronic ischemic heart disease in patients. ..
  6. CX43 IN A GENETIC MODEL OF ALTERED MYOCARDIAL CONDUCTION
    Jeffrey Saffitz; Fiscal Year: 2000
    ....