Consequences of pressure overload on sarcomere protein mutation-induced
hypertrophic cardiomyopathy
J. Schmitt, C. Semsarian, M. Arad, J. Gannon, F. Ahmad, C. Duffy, R. Lee, C. Seidman, и J. Seidman. Circulation, 108 (9):
1133-8(сентября 2003)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..
Аннотация
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.
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.
%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
}