Research Topics
| Jeffrey SaffitzSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
The pathobiology of arrhythmogenic cardiomyopathyJeffrey 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....- Arrhythmogenic right ventricular cardiomyopathy: new insights into disease mechanisms and diagnosisJeffrey 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... - Arrhythmogenic cardiomyopathy and abnormalities of cell-to-cell couplingJeffrey E Saffitz
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Heart Rhythm 6:S62-5. 2009.... 
Remodeling of gap junctions in ischemic and nonischemic forms of heart diseaseJeffrey 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...- Adhesion molecules: why they are important to the electrophysiologistJeffrey E Saffitz
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Cardiovasc Electrophysiol 17:225-9. 2006 - Douglas P. Zipes Lecture. Biology and pathobiology of cardiac connexins: from cell to bedsideJeffrey 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... - Metastatic peritoneal mesothelioma in the setting of recurrent ascites: a case reportVon Samedi
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts 02215 5400, USA
Diagn Cytopathol 38:675-81. 2010.... - Dependence of electrical coupling on mechanical coupling in cardiac myocytes: insights gained from cardiomyopathies caused by defects in cell-cell connectionsJeffrey 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... - A new diagnostic test for arrhythmogenic right ventricular cardiomyopathyAngeliki 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... - Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathyJoseph 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.... - Distinct pathways regulate expression of cardiac electrical and mechanical junction proteins in response to stretchKiyomi 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... - Arrhythmogenic right ventricular cardiomyopathy: new insights into mechanisms of diseaseJeffrey E Saffitz
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
Cardiovasc Pathol 19:166-70. 2010.... - The pathology of sudden cardiac death in patients with ischemic heart disease--arrhythmology for anatomic pathologistsJeffrey 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... - Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human heartsMichael 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... - Mechanisms of delayed electrical uncoupling induced by ischemic preconditioningSandeep 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... - Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathyZhao 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... - Relative contributions of connexins 40 and 43 to atrial impulse propagation in synthetic strands of neonatal and fetal murine cardiomyocytesPhilippe Beauchamp
Department of Physiology, University of Bern, Switzerland
Circ Res 99:1216-24. 2006.... - c-Jun N-terminal kinase activation mediates downregulation of connexin43 in cardiomyocytesBrian 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... - Targeted activation of c-Jun N-terminal kinase in vivo induces restrictive cardiomyopathy and conduction defectsBrian 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... - Redistribution of connexin45 in gap junctions of connexin43-deficient heartsCarolyn 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... - Effects of mechanical forces and mediators of hypertrophy on remodeling of gap junctions in the heartJeffrey 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... - 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.... - Electrical propagation in synthetic ventricular myocyte strands from germline connexin43 knockout micePhilippe 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... 
Protein kinase Cepsilon mediates salutary effects on electrical coupling induced by ischemic preconditioningThomas 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...- A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathyAngeliki 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... - Transmural distribution of connexins in rodent heartsKathryn 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... - Autocrine regulation of myocyte Cx43 expression by VEGFRhea 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... - Spontaneous and inducible ventricular arrhythmias after myocardial infarction in miceTetsuo Betsuyaku
Department of Medicine (Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110, USA
Cardiovasc Pathol 13:156-64. 2004..Mice with MI exhibit increased arrhythmias. However, reduced coupling in Cx43-deficient mice does not significantly enhance spontaneous or inducible VT after MI... - Connexin43 as a determinant of myocardial infarct size following coronary occlusion in miceShigeto 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..New therapies designed to decrease the risk of arrhythmias by enhancing intercellular communication could lead to larger infarcts caused by persistent coronary occlusion... - Mechanoelectrical feedback as novel mechanism of cardiac electrical remodelingDarwin 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... - Diminished zonula occludens-1 expression in the failing human heartJames 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... - Dramatic accumulation of triglycerides and precipitation of cardiac hemodynamic dysfunction during brief caloric restriction in transgenic myocardium expressing human calcium-independent phospholipase A2gammaDavid 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.... - Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosisAtsushi 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... - Matrix-protein-specific regulation of Cx43 expression in cardiac myocytes subjected to mechanical loadAmit 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... - Connexins, conduction, and atrial fibrillationJeffrey E Saffitz
N Engl J Med 354:2712-4. 2006 - Impulse propagation in synthetic strands of neonatal cardiac myocytes with genetically reduced levels of connexin43Stuart 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... - Structural heart disease, SCN5A gene mutations, and Brugada syndrome: a complex ménage à troisJeffrey E Saffitz
Circulation 112:3672-4. 2005 - Extracardiac progenitor cells repopulate most major cell types in the transplanted human heartElina Minami
Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
Circulation 112:2951-8. 2005..The high degree of endothelial chimerism may have immune implications such as for myocardial rejection or graft vasculopathy... - 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 mannerLaurie K Russell
Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
Circ Res 94:525-33. 2004....
Research Grants
- Disease Mechanisms in ARVCJeffrey E Saffitz; Fiscal Year: 2010..Our ultimate goal is to help develop mechanism-based therapies to prevent sudden death. ..
- REGULATION OF MYOCARDIAL GAP JUNCTIONSJeffrey Saffitz; Fiscal Year: 2002..The results of the proposed research will provide new insights into fundamental mechanisms of arrhythmogenesis in heart failure. ..
- REGULATION OF MYOCARDIAL GAP JUNCTIONSJeffrey 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. ..
- REGULATION OF MYOCARDIAL GAP JUNCTIONSJeffrey Saffitz; Fiscal Year: 2006..abstract_text> ..
- CX43 IN A GENETIC MODEL OF ALTERED MYOCARDIAL CONDUCTIONJeffrey 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. ..
- CX43 IN A GENETIC MODEL OF ALTERED MYOCARDIAL CONDUCTIONJeffrey Saffitz; Fiscal Year: 2000....