%0 Journal Article %1 Schmitt2003a %A Schmitt, J. P. %A Semsarian, C. %A Arad, M. %A Gannon, J. %A Ahmad, F. %A Duffy, C. %A Lee, R. T. %A Seidman, C. E. %A Seidman, J. G. %D 2003 %J Circulation %K Hemodynamics %N 9 %P 1133-8 %T Consequences of pressure overload on sarcomere protein mutation-induced hypertrophic cardiomyopathy %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12925456 %V 108 %X BACKGROUND: Whether ventricular remodeling from hypertrophic cardiomyopathy (HCM), systemic hypertension, or other pathologies arises through a common signaling pathway or through independent molecular mechanisms is unknown. To study this, we assessed cardiac hypertrophy in a mouse model of HCM subjected to increased left ventricular (LV) load. METHODS AND RESULTS: Transverse aortic banding of mice with or without an Arg403Gln cardiac myosin heavy chain mutation (alphaMHC403/+) produced similarly elevated LV pressures (120+/-30 versus 112+/-14 mm Hg; P=NS). No mice developed heart failure, and mortality (26% alphaMHC403/+, 35% wild-type) was comparable. Load-induced hypertrophy was identical in banded 129SvEv alphaMHC403/+ mice (LV anterior wall LVAW=1.28+/-0.11) and 129SvEv wild-type mice (LVAW=1.29+/-0.11 mm; P=NS). Genetically outbred Black Swiss (BS) alphaMHC403/+ mice showed only mildly exaggerated hypertrophy in response to aortic banding (BS alphaMHC403/+ LVAW=1.30+/-0.13 mm; BS wild-type LVAW=1.17+/-0.15 mm; P=0.03), suggesting some effect from a BS genetic locus that modifies hypertrophy induced by the cardiac MHC Arg403Gln mutation. Histopathology and molecular markers of hypertrophy were comparable in all banded 129SvEv or BS mice. Banded alphaMHC403/+ mice had potential for greater hypertrophy, because cyclosporin A treatment markedly augmented hypertrophy. CONCLUSIONS: The uniform hypertrophic response to increased ventricular load in wild-type and alphaMHC403/+ mice indicates independent cardiac remodeling pathways and predicts that coexistent hypertension and HCM should not profoundly exacerbate cardiac hypertrophy. In contrast, sarcomere mutation and cyclosporin A-mediated calcineurin inhibition stimulate a shared hypertrophic signaling pathway. Defining distinct signaling pathways that trigger myocyte growth should help to tailor therapies for cardiac hypertrophy.

@article{Schmitt2003a, abstract = {BACKGROUND: Whether ventricular remodeling from hypertrophic cardiomyopathy (HCM), systemic hypertension, or other pathologies arises through a common signaling pathway or through independent molecular mechanisms is unknown. To study this, we assessed cardiac hypertrophy in a mouse model of HCM subjected to increased left ventricular (LV) load. METHODS AND RESULTS: Transverse aortic banding of mice with or without an Arg403Gln cardiac myosin heavy chain mutation (alphaMHC403/+) produced similarly elevated LV pressures (120+/-30 versus 112+/-14 mm Hg; P=NS). No mice developed heart failure, and mortality (26% alphaMHC403/+, 35% wild-type) was comparable. Load-induced hypertrophy was identical in banded 129SvEv alphaMHC403/+ mice (LV anterior wall LVAW=1.28+/-0.11) and 129SvEv wild-type mice (LVAW=1.29+/-0.11 mm; P=NS). Genetically outbred Black Swiss (BS) alphaMHC403/+ mice showed only mildly exaggerated hypertrophy in response to aortic banding (BS alphaMHC403/+ LVAW=1.30+/-0.13 mm; BS wild-type LVAW=1.17+/-0.15 mm; P=0.03), suggesting some effect from a BS genetic locus that modifies hypertrophy induced by the cardiac MHC Arg403Gln mutation. Histopathology and molecular markers of hypertrophy were comparable in all banded 129SvEv or BS mice. Banded alphaMHC403/+ mice had potential for greater hypertrophy, because cyclosporin A treatment markedly augmented hypertrophy. CONCLUSIONS: The uniform hypertrophic response to increased ventricular load in wild-type and alphaMHC403/+ mice indicates independent cardiac remodeling pathways and predicts that coexistent hypertension and HCM should not profoundly exacerbate cardiac hypertrophy. In contrast, sarcomere mutation and cyclosporin A-mediated calcineurin inhibition stimulate a shared hypertrophic signaling pathway. Defining distinct signaling pathways that trigger myocyte growth should help to tailor therapies for cardiac hypertrophy.}, added-at = {2018-07-29T23:22:21.000+0200}, author = {Schmitt, J. P. and Semsarian, C. and Arad, M. and Gannon, J. and Ahmad, F. and Duffy, C. and Lee, R. T. and Seidman, C. E. and Seidman, J. G.}, biburl = {https://www.bibsonomy.org/bibtex/208dd1f482cfc6599dcba964eda185e3e/freefattyacids}, endnotereftype = {Journal Article}, interhash = {0c24b097ba0d3ba63f96fe622653fb18}, intrahash = {08dd1f482cfc6599dcba964eda185e3e}, issn = {1524-4539 (Electronic) 1524-4539 (Linking)}, journal = {Circulation}, keywords = {Hemodynamics}, month = {Sep 2}, note = {Schmitt, Joachim P Semsarian, Christopher Arad, Michael Gannon, Joseph Ahmad, Ferhaan Duffy, Catherine Lee, Richard T Seidman, Christine E Seidman, J G Research Support, Non-U.S. Gov't United States Circulation Circulation. 2003 Sep 2;108(9):1133-8. Epub 2003 Aug 18.}, number = 9, pages = {1133-8}, shorttitle = {Consequences of pressure overload on sarcomere protein mutation-induced hypertrophic cardiomyopathy}, timestamp = {2018-07-29T23:22:21.000+0200}, title = {Consequences of pressure overload on sarcomere protein mutation-induced hypertrophic cardiomyopathy}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12925456}, volume = 108, year = 2003 }