title: PGC-1β deficiency accelerates the transition to heart failure in pressure overload hypertrophy.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Riehle
authors.forename: Adam R
authors.initials: AR
authors.lastname: Wende
authors.forename: Vlad G
authors.initials: VG
authors.lastname: Zaha
authors.forename: Karla Maria
authors.initials: KM
authors.lastname: Pires
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wayment
authors.forename: Curtis
authors.initials: C
authors.lastname: Olsen
authors.forename: Heiko
authors.initials: H
authors.lastname: Bugger
authors.forename: Jonathan
authors.initials: J
authors.lastname: Buchanan
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Annie Bello
authors.initials: AB
authors.lastname: Moreira
authors.forename: Torsten
authors.initials: T
authors.lastname: Doenst
authors.forename: Gema
authors.initials: G
authors.lastname: Medina-Gomez
authors.forename: Sheldon E
authors.initials: SE
authors.lastname: Litwin
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lelliott
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
authors.forename: E Dale
authors.initials: ED
authors.lastname: Abel
mesh_terms: D000375:Aging; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D018450:Disease Progression; D004734:Energy Metabolism / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D006593:Hexokinase / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014157:Transcription Factors; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left
chemical_list: D005227:Fatty Acids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D006593:Hexokinase; D005947:Glucose