The NF-kappa B Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis

Research output: Contribution to journalArticle

Standard

The NF-kappa B Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis. / Gaspar-Pereira, S; Fullard, N; Townsend, PA; Banks, PS; Ellis, EL; Fox, C; Maxwell, AG; Murphy, LB; Kirk, A; Bauer, R; Caamano, Jorge; Figg, N; Foo, RS; Mann, J; Mann, DA; Oakley, F.

In: The American Journal of Pathology, Vol. 180, No. 3, 01.03.2012, p. 929-939.

Research output: Contribution to journalArticle

Harvard

Gaspar-Pereira, S, Fullard, N, Townsend, PA, Banks, PS, Ellis, EL, Fox, C, Maxwell, AG, Murphy, LB, Kirk, A, Bauer, R, Caamano, J, Figg, N, Foo, RS, Mann, J, Mann, DA & Oakley, F 2012, 'The NF-kappa B Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis', The American Journal of Pathology, vol. 180, no. 3, pp. 929-939. https://doi.org/10.1016/j.ajpath.2011.11.007

APA

Gaspar-Pereira, S., Fullard, N., Townsend, PA., Banks, PS., Ellis, EL., Fox, C., Maxwell, AG., Murphy, LB., Kirk, A., Bauer, R., Caamano, J., Figg, N., Foo, RS., Mann, J., Mann, DA., & Oakley, F. (2012). The NF-kappa B Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis. The American Journal of Pathology, 180(3), 929-939. https://doi.org/10.1016/j.ajpath.2011.11.007

Vancouver

Gaspar-Pereira S, Fullard N, Townsend PA, Banks PS, Ellis EL, Fox C et al. The NF-kappa B Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis. The American Journal of Pathology. 2012 Mar 1;180(3):929-939. https://doi.org/10.1016/j.ajpath.2011.11.007

Author

Gaspar-Pereira, S ; Fullard, N ; Townsend, PA ; Banks, PS ; Ellis, EL ; Fox, C ; Maxwell, AG ; Murphy, LB ; Kirk, A ; Bauer, R ; Caamano, Jorge ; Figg, N ; Foo, RS ; Mann, J ; Mann, DA ; Oakley, F. / The NF-kappa B Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis. In: The American Journal of Pathology. 2012 ; Vol. 180, No. 3. pp. 929-939.

Bibtex

@article{875ddcffe2c14dc49b82048c1dfa0e11,
title = "The NF-kappa B Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis",
abstract = "Cardiac remodeling and hypertrophy are the pathological consequences of cardiovascular disease and are correlated with its associated mortality. Activity of the transcription factor NF-kappa B is increased in the diseased heart; however, our present understanding of how the individual subunits contribute to cardiovascular disease is limited. We assign a new role for the c-Rel subunit as a stimulator of cardiac hypertrophy and fibrosis. We discovered that c-Rel-deficient mice have smaller hearts at birth, as well as during adult-hood, and are protected from developing cardiac hypertrophy and fibrosis after chronic angiotensin infusion. Results of both gene expression and cross-linked chromatin immunoprecipitation assay analyses identified transcriptional activators of hypertrophy, myocyte enhancer family, Gata4, and Tbx proteins as Rel gene targets. We suggest that the p50 subunit could limit the prohypertrophic actions of c-Rel in the normal heart, because p50 overexpression in H9c2 cells repressed c-Rel levels and the absence of cardiac p50 was associated with increases in both c-Rel levels and cardiac hypertrophy. We report for the first time that c-Rel is highly expressed and confined to the nuclei of diseased adult human hearts but is restricted to the cytoplasm of normal cardiac tissues. We conclude that c-Rel-dependent signaling is critical for both cardiac remodeling and hypertrophy. Targeting its activities could offer a novel therapeutic strategy to limit the effects of cardiac disease. (Am J Pathol 2012, 180:929-939; DOI. 10.1016/j.ajpath.2011.11.007)",
author = "S Gaspar-Pereira and N Fullard and PA Townsend and PS Banks and EL Ellis and C Fox and AG Maxwell and LB Murphy and A Kirk and R Bauer and Jorge Caamano and N Figg and RS Foo and J Mann and DA Mann and F Oakley",
year = "2012",
month = mar,
day = "1",
doi = "10.1016/j.ajpath.2011.11.007",
language = "English",
volume = "180",
pages = "929--939",
journal = "The American Journal of Pathology",
issn = "0002-9440",
publisher = "American Society for Investigative Pathology",
number = "3",

}

RIS

TY - JOUR

T1 - The NF-kappa B Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis

AU - Gaspar-Pereira, S

AU - Fullard, N

AU - Townsend, PA

AU - Banks, PS

AU - Ellis, EL

AU - Fox, C

AU - Maxwell, AG

AU - Murphy, LB

AU - Kirk, A

AU - Bauer, R

AU - Caamano, Jorge

AU - Figg, N

AU - Foo, RS

AU - Mann, J

AU - Mann, DA

AU - Oakley, F

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Cardiac remodeling and hypertrophy are the pathological consequences of cardiovascular disease and are correlated with its associated mortality. Activity of the transcription factor NF-kappa B is increased in the diseased heart; however, our present understanding of how the individual subunits contribute to cardiovascular disease is limited. We assign a new role for the c-Rel subunit as a stimulator of cardiac hypertrophy and fibrosis. We discovered that c-Rel-deficient mice have smaller hearts at birth, as well as during adult-hood, and are protected from developing cardiac hypertrophy and fibrosis after chronic angiotensin infusion. Results of both gene expression and cross-linked chromatin immunoprecipitation assay analyses identified transcriptional activators of hypertrophy, myocyte enhancer family, Gata4, and Tbx proteins as Rel gene targets. We suggest that the p50 subunit could limit the prohypertrophic actions of c-Rel in the normal heart, because p50 overexpression in H9c2 cells repressed c-Rel levels and the absence of cardiac p50 was associated with increases in both c-Rel levels and cardiac hypertrophy. We report for the first time that c-Rel is highly expressed and confined to the nuclei of diseased adult human hearts but is restricted to the cytoplasm of normal cardiac tissues. We conclude that c-Rel-dependent signaling is critical for both cardiac remodeling and hypertrophy. Targeting its activities could offer a novel therapeutic strategy to limit the effects of cardiac disease. (Am J Pathol 2012, 180:929-939; DOI. 10.1016/j.ajpath.2011.11.007)

AB - Cardiac remodeling and hypertrophy are the pathological consequences of cardiovascular disease and are correlated with its associated mortality. Activity of the transcription factor NF-kappa B is increased in the diseased heart; however, our present understanding of how the individual subunits contribute to cardiovascular disease is limited. We assign a new role for the c-Rel subunit as a stimulator of cardiac hypertrophy and fibrosis. We discovered that c-Rel-deficient mice have smaller hearts at birth, as well as during adult-hood, and are protected from developing cardiac hypertrophy and fibrosis after chronic angiotensin infusion. Results of both gene expression and cross-linked chromatin immunoprecipitation assay analyses identified transcriptional activators of hypertrophy, myocyte enhancer family, Gata4, and Tbx proteins as Rel gene targets. We suggest that the p50 subunit could limit the prohypertrophic actions of c-Rel in the normal heart, because p50 overexpression in H9c2 cells repressed c-Rel levels and the absence of cardiac p50 was associated with increases in both c-Rel levels and cardiac hypertrophy. We report for the first time that c-Rel is highly expressed and confined to the nuclei of diseased adult human hearts but is restricted to the cytoplasm of normal cardiac tissues. We conclude that c-Rel-dependent signaling is critical for both cardiac remodeling and hypertrophy. Targeting its activities could offer a novel therapeutic strategy to limit the effects of cardiac disease. (Am J Pathol 2012, 180:929-939; DOI. 10.1016/j.ajpath.2011.11.007)

U2 - 10.1016/j.ajpath.2011.11.007

DO - 10.1016/j.ajpath.2011.11.007

M3 - Article

C2 - 22210479

VL - 180

SP - 929

EP - 939

JO - The American Journal of Pathology

JF - The American Journal of Pathology

SN - 0002-9440

IS - 3

ER -