title: Altered myofilament stoichiometry in response to heart failure in a cardioprotective α-myosin heavy chain transgenic rabbit model.
abstract: OBJECTIVE
  Decreases in α myosin heavy chain (α-MHC) is a common feature of human heart failure (HF), whereas α-MHC overexpression in transgenic (TG) rabbits is cardioprotective against tachycardia-induced cardiomyopathy (TIC). Hypothesizing that MHC isoform content alterations would impact sarcomere and mitochondrial energetics protein complement, we investigated the impact of α-MHC overexpression on global cardiac protein expression.
  
  
  METHODS
  Protein expression was assessed by two-dimensional gel electrophoresis and MS on the extracts from TG and nontransgenic (NTG) rabbits under TIC or sham-operated conditions.
  
  
  RESULTS
  We observed significant changes in the levels of actin, myosin light chain 2, and desmin between the left ventricular (LV) tissue of TG and NTG animals. The proteome was broadly impacted, with significant changes in mitochondrial energetics and chaperone protein families. No changes were observed in total cellular MHC or in myofibril-associated MHC. In myofibrils isolated from TG(sham) animals, only actin levels were altered in TG(sham) compared with NTG(sham) animals, suggesting careful myofibril assembly regulation.
  
  
  CONCLUSIONS
  These data suggest that myofibril protein composition may protect against TIC, emphasizing protein interconnectivity and demonstrating the need for broad-based proteomic studies in understanding targeted genetic manipulations. This study identifies the targets for future development of cardioprotective agents and elucidates tachycardia-induced heart failure pathways.
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Stanley
authors.forename: David R
authors.initials: DR
authors.lastname: Graham
authors.forename: Jeanne
authors.initials: J
authors.lastname: James
authors.forename: Megan
authors.initials: M
authors.lastname: Mitsak
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Tarwater
authors.forename: Jeff
authors.initials: J
authors.lastname: Robbins
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Van Eyk
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D006333:Heart Failure / Q000378:metabolism*; D013058:Mass Spectrometry; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D040901:Proteomics; D011817:Rabbits
chemical_list: D020543:Proteome; D018995:Myosin Heavy Chains