title: Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.
abstract: BACKGROUND
  In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking.
  
  
  METHODS
  We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples.
  
  
  RESULTS
  We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function.
  
  
  CONCLUSIONS
  These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Cristi L
authors.initials: CL
authors.lastname: Galindo
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Soslow
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas.
authors.forename: Candice L
authors.initials: CL
authors.lastname: Brinkmeyer-Langford
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Manisha
authors.initials: M
authors.lastname: Gupte
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Smith
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Seng
authors.initials: S
authors.lastname: Sengsayadeth
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Sawyer
authors.affiliation: Department of Pediatrics, Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
authors.forename: D Woodrow
authors.initials: DW
authors.lastname: Benson
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas.
authors.forename: Joe N
authors.initials: JN
authors.lastname: Kornegay
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.|Department of Pediatrics, Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Markham
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D004285:Dogs; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D018482:Muscle, Skeletal / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D015415:Biomarkers