Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia Export

@article{citeulike:781856, abstract = {Sarcomere protein gene mutations cause hypertrophic cardiomyopathy (HCM), a disease with distinctive histopathology and increased susceptibility to cardiac arrhythmias and risk for sudden death. Myocyte disarray (disorganized cell-cell contact) and cardiac fibrosis, the prototypic but protean features of HCM histopathology, are presumed triggers for ventricular arrhythmias that precipitate sudden death events. To assess relationships between arrhythmias and HCM pathology without confounding human variables, such as genetic heterogeneity of disease-causing mutations, background genotypes, and lifestyles, we studied cardiac electrophysiology, hypertrophy, and histopathology in mice engineered to carry an HCM mutation. Both genetically outbred and inbred HCM mice had variable susceptibility to arrhythmias, differences in ventricular hypertrophy, and variable amounts and distribution of histopathology. Among inbred HCM mice, neither the extent nor location of myocyte disarray or cardiac fibrosis correlated with ex vivo signal conduction properties or in vivo electrophysiologically stimulated arrhythmias. In contrast, the amount of ventricular hypertrophy was significantly associated with increased arrhythmia susceptibility. These data demonstrate that distinct somatic events contribute to variable HCM pathology and that cardiac hypertrophy, more than fibrosis or disarray, correlates with arrhythmic risk. We suggest that a shared pathway triggered by sarcomere gene mutations links cardiac hypertrophy and arrhythmias in HCM. 10.1073/pnas.0509145102}, author = {Wolf, Cordula M. and Moskowitz, Ivan P. and Arno, Scott and Branco, Dorothy M. and Semsarian, Christopher and Bernstein, Scott A. and Peterson, Michael and Maida, Michael and Morley, Gregory E. and Fishman, Glenn and Berul, Charles I. and Seidman, Christine E. and Seidman, J. G.}, citeulike-article-id = {781856}, citeulike-linkout-0 = {http://www.pnas.org/cgi/content/abstract/102/50/18123}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16332958}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16332958}, day = {13}, journal = {PNAS}, keywords = {arrhythmia, hypertrophy}, month = {December}, number = {50}, pages = {18123--18128}, posted-at = {2006-08-01 19:25:49}, priority = {2}, title = {Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia}, url = {http://www.pnas.org/cgi/content/abstract/102/50/18123}, volume = {102}, year = {2005} }

TY - JOUR ID - citeulike:781856 L3 - citeulike-article-id:781856 N2 - Sarcomere protein gene mutations cause hypertrophic cardiomyopathy (HCM), a disease with distinctive histopathology and increased susceptibility to cardiac arrhythmias and risk for sudden death. Myocyte disarray (disorganized cell-cell contact) and cardiac fibrosis, the prototypic but protean features of HCM histopathology, are presumed triggers for ventricular arrhythmias that precipitate sudden death events. To assess relationships between arrhythmias and HCM pathology without confounding human variables, such as genetic heterogeneity of disease-causing mutations, background genotypes, and lifestyles, we studied cardiac electrophysiology, hypertrophy, and histopathology in mice engineered to carry an HCM mutation. Both genetically outbred and inbred HCM mice had variable susceptibility to arrhythmias, differences in ventricular hypertrophy, and variable amounts and distribution of histopathology. Among inbred HCM mice, neither the extent nor location of myocyte disarray or cardiac fibrosis correlated with ex vivo signal conduction properties or in vivo electrophysiologically stimulated arrhythmias. In contrast, the amount of ventricular hypertrophy was significantly associated with increased arrhythmia susceptibility. These data demonstrate that distinct somatic events contribute to variable HCM pathology and that cardiac hypertrophy, more than fibrosis or disarray, correlates with arrhythmic risk. We suggest that a shared pathway triggered by sarcomere gene mutations links cardiac hypertrophy and arrhythmias in HCM. 10.1073/pnas.0509145102 IS - 50 JF - PNAS EP - 18128 TI - Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia VL - 102 SP - 18123 KW - arrhythmia KW - hypertrophy AU - Wolf, Cordula AU - Moskowitz, Ivan AU - Arno, Scott AU - Branco, Dorothy AU - Semsarian, Christopher AU - Bernstein, Scott AU - Peterson, Michael AU - Maida, Michael AU - Morley, Gregory AU - Fishman, Glenn AU - Berul, Charles AU - Seidman, Christine AU - Seidman, JG PY - 2005/12/13/ UR - http://www.pnas.org/cgi/content/abstract/102/50/18123 ER -