PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy

Christian Riehle, Adam R. Wende, Vlad G. Zaha, Karla Maria Pires, Benjamin Wayment, Curtis Olsen, Heiko Bugger, Jonathan Buchanan, Xiaohui Wang, Annie Bello Moreira, Torsten Doenst, Gema Medina-Gomez, Sheldon E. Litwin, Christopher J. Lelliott, Antonio Vidal-Puig, E. Dale Abel

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Rationale: Pressure overload cardiac hypertrophy, a risk factor for heart failure, is associated with reduced mitochondrial fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) proteins that correlate in rodents with reduced PGC-1α expression. Objective: To determine the role of PGC-1β in maintaining mitochondrial energy metabolism and contractile function in pressure overload hypertrophy. Methods and Results: PGC-1β deficient (KO) mice and wildtype (WT) controls were subjected to transverse aortic constriction (TAC). Although LV function was modestly reduced in young KO hearts, there was no further decline with age so that LV function was similar between KO and WT when TAC was performed. WT-TAC mice developed relatively compensated LVH, despite reduced mitochondrial function and repression of OXPHOS and FAO genes. In nonstressed KO hearts, OXPHOS gene expression and palmitoyl-carnitine- supported mitochondrial function were reduced to the same extent as banded WT, but FAO gene expression was normal. Following TAC, KO mice progressed more rapidly to heart failure and developed more severe mitochondrial dysfunction, despite a similar overall pattern of repression of OXPHOS and FAO genes as WT-TAC. However, in relation to WT-TAC, PGC-1β deficient mice exhibited greater degrees of oxidative stress, decreased cardiac efficiency, lower rates of glucose metabolism, and repression of hexokinase II protein. Conclusions: PGC-1β plays an important role in maintaining baseline mitochondrial function and cardiac contractile function following pressure overload hypertrophy by preserving glucose metabolism and preventing oxidative stress.

Original languageEnglish (US)
Pages (from-to)783-793
Number of pages11
JournalCirculation Research
Volume109
Issue number7
DOIs
StatePublished - Sep 16 2011

Fingerprint

Constriction
Hypertrophy
Heart Failure
Oxidative Phosphorylation
Pressure
Fatty Acids
Oxidative Stress
Gene Expression
Glucose
Hexokinase
Carnitine
Cardiomegaly
Energy Metabolism
Genes
Rodentia
Proteins

Keywords

  • cardiac hypertrophy
  • gene expression
  • heart failure
  • mitochondria

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy. / Riehle, Christian; Wende, Adam R.; Zaha, Vlad G.; Pires, Karla Maria; Wayment, Benjamin; Olsen, Curtis; Bugger, Heiko; Buchanan, Jonathan; Wang, Xiaohui; Moreira, Annie Bello; Doenst, Torsten; Medina-Gomez, Gema; Litwin, Sheldon E.; Lelliott, Christopher J.; Vidal-Puig, Antonio; Abel, E. Dale.

In: Circulation Research, Vol. 109, No. 7, 16.09.2011, p. 783-793.

Research output: Contribution to journalArticle

Riehle, C, Wende, AR, Zaha, VG, Pires, KM, Wayment, B, Olsen, C, Bugger, H, Buchanan, J, Wang, X, Moreira, AB, Doenst, T, Medina-Gomez, G, Litwin, SE, Lelliott, CJ, Vidal-Puig, A & Abel, ED 2011, 'PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy', Circulation Research, vol. 109, no. 7, pp. 783-793. https://doi.org/10.1161/CIRCRESAHA.111.243964
Riehle, Christian ; Wende, Adam R. ; Zaha, Vlad G. ; Pires, Karla Maria ; Wayment, Benjamin ; Olsen, Curtis ; Bugger, Heiko ; Buchanan, Jonathan ; Wang, Xiaohui ; Moreira, Annie Bello ; Doenst, Torsten ; Medina-Gomez, Gema ; Litwin, Sheldon E. ; Lelliott, Christopher J. ; Vidal-Puig, Antonio ; Abel, E. Dale. / PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy. In: Circulation Research. 2011 ; Vol. 109, No. 7. pp. 783-793.
@article{7be890c632ac4fb5b7a289647c6b2acc,
title = "PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy",
abstract = "Rationale: Pressure overload cardiac hypertrophy, a risk factor for heart failure, is associated with reduced mitochondrial fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) proteins that correlate in rodents with reduced PGC-1α expression. Objective: To determine the role of PGC-1β in maintaining mitochondrial energy metabolism and contractile function in pressure overload hypertrophy. Methods and Results: PGC-1β deficient (KO) mice and wildtype (WT) controls were subjected to transverse aortic constriction (TAC). Although LV function was modestly reduced in young KO hearts, there was no further decline with age so that LV function was similar between KO and WT when TAC was performed. WT-TAC mice developed relatively compensated LVH, despite reduced mitochondrial function and repression of OXPHOS and FAO genes. In nonstressed KO hearts, OXPHOS gene expression and palmitoyl-carnitine- supported mitochondrial function were reduced to the same extent as banded WT, but FAO gene expression was normal. Following TAC, KO mice progressed more rapidly to heart failure and developed more severe mitochondrial dysfunction, despite a similar overall pattern of repression of OXPHOS and FAO genes as WT-TAC. However, in relation to WT-TAC, PGC-1β deficient mice exhibited greater degrees of oxidative stress, decreased cardiac efficiency, lower rates of glucose metabolism, and repression of hexokinase II protein. Conclusions: PGC-1β plays an important role in maintaining baseline mitochondrial function and cardiac contractile function following pressure overload hypertrophy by preserving glucose metabolism and preventing oxidative stress.",
keywords = "cardiac hypertrophy, gene expression, heart failure, mitochondria",
author = "Christian Riehle and Wende, {Adam R.} and Zaha, {Vlad G.} and Pires, {Karla Maria} and Benjamin Wayment and Curtis Olsen and Heiko Bugger and Jonathan Buchanan and Xiaohui Wang and Moreira, {Annie Bello} and Torsten Doenst and Gema Medina-Gomez and Litwin, {Sheldon E.} and Lelliott, {Christopher J.} and Antonio Vidal-Puig and Abel, {E. Dale}",
year = "2011",
month = "9",
day = "16",
doi = "10.1161/CIRCRESAHA.111.243964",
language = "English (US)",
volume = "109",
pages = "783--793",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy

AU - Riehle, Christian

AU - Wende, Adam R.

AU - Zaha, Vlad G.

AU - Pires, Karla Maria

AU - Wayment, Benjamin

AU - Olsen, Curtis

AU - Bugger, Heiko

AU - Buchanan, Jonathan

AU - Wang, Xiaohui

AU - Moreira, Annie Bello

AU - Doenst, Torsten

AU - Medina-Gomez, Gema

AU - Litwin, Sheldon E.

AU - Lelliott, Christopher J.

AU - Vidal-Puig, Antonio

AU - Abel, E. Dale

PY - 2011/9/16

Y1 - 2011/9/16

N2 - Rationale: Pressure overload cardiac hypertrophy, a risk factor for heart failure, is associated with reduced mitochondrial fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) proteins that correlate in rodents with reduced PGC-1α expression. Objective: To determine the role of PGC-1β in maintaining mitochondrial energy metabolism and contractile function in pressure overload hypertrophy. Methods and Results: PGC-1β deficient (KO) mice and wildtype (WT) controls were subjected to transverse aortic constriction (TAC). Although LV function was modestly reduced in young KO hearts, there was no further decline with age so that LV function was similar between KO and WT when TAC was performed. WT-TAC mice developed relatively compensated LVH, despite reduced mitochondrial function and repression of OXPHOS and FAO genes. In nonstressed KO hearts, OXPHOS gene expression and palmitoyl-carnitine- supported mitochondrial function were reduced to the same extent as banded WT, but FAO gene expression was normal. Following TAC, KO mice progressed more rapidly to heart failure and developed more severe mitochondrial dysfunction, despite a similar overall pattern of repression of OXPHOS and FAO genes as WT-TAC. However, in relation to WT-TAC, PGC-1β deficient mice exhibited greater degrees of oxidative stress, decreased cardiac efficiency, lower rates of glucose metabolism, and repression of hexokinase II protein. Conclusions: PGC-1β plays an important role in maintaining baseline mitochondrial function and cardiac contractile function following pressure overload hypertrophy by preserving glucose metabolism and preventing oxidative stress.

AB - Rationale: Pressure overload cardiac hypertrophy, a risk factor for heart failure, is associated with reduced mitochondrial fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) proteins that correlate in rodents with reduced PGC-1α expression. Objective: To determine the role of PGC-1β in maintaining mitochondrial energy metabolism and contractile function in pressure overload hypertrophy. Methods and Results: PGC-1β deficient (KO) mice and wildtype (WT) controls were subjected to transverse aortic constriction (TAC). Although LV function was modestly reduced in young KO hearts, there was no further decline with age so that LV function was similar between KO and WT when TAC was performed. WT-TAC mice developed relatively compensated LVH, despite reduced mitochondrial function and repression of OXPHOS and FAO genes. In nonstressed KO hearts, OXPHOS gene expression and palmitoyl-carnitine- supported mitochondrial function were reduced to the same extent as banded WT, but FAO gene expression was normal. Following TAC, KO mice progressed more rapidly to heart failure and developed more severe mitochondrial dysfunction, despite a similar overall pattern of repression of OXPHOS and FAO genes as WT-TAC. However, in relation to WT-TAC, PGC-1β deficient mice exhibited greater degrees of oxidative stress, decreased cardiac efficiency, lower rates of glucose metabolism, and repression of hexokinase II protein. Conclusions: PGC-1β plays an important role in maintaining baseline mitochondrial function and cardiac contractile function following pressure overload hypertrophy by preserving glucose metabolism and preventing oxidative stress.

KW - cardiac hypertrophy

KW - gene expression

KW - heart failure

KW - mitochondria

UR - http://www.scopus.com/inward/record.url?scp=80052970004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052970004&partnerID=8YFLogxK

U2 - 10.1161/CIRCRESAHA.111.243964

DO - 10.1161/CIRCRESAHA.111.243964

M3 - Article

C2 - 21799152

AN - SCOPUS:80052970004

VL - 109

SP - 783

EP - 793

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 7

ER -