PMID- 26672735 OWN - NLM STAT- MEDLINE DCOM- 20170130 LR - 20191210 IS - 1530-0447 (Electronic) IS - 0031-3998 (Print) IS - 0031-3998 (Linking) VI - 79 IP - 4 DP - 2016 Apr TI - Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy. PG - 629-36 LID - 10.1038/pr.2015.257 [doi] AB - 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. CONCLUSION: 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. FAU - Galindo, Cristi L AU - Galindo CL AD - Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Soslow, Jonathan H AU - Soslow JH AD - Department of Pediatrics, Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Brinkmeyer-Langford, Candice L AU - Brinkmeyer-Langford CL AD - Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas. FAU - Gupte, Manisha AU - Gupte M AD - Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Smith, Holly M AU - Smith HM AD - Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Sengsayadeth, Seng AU - Sengsayadeth S AD - Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Sawyer, Douglas B AU - Sawyer DB AD - Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Benson, D Woodrow AU - Benson DW AD - Department of Pediatrics, Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee, Wisconsin. FAU - Kornegay, Joe N AU - Kornegay JN AD - Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas. FAU - Markham, Larry W AU - Markham LW AD - Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. AD - Department of Pediatrics, Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, Tennessee. LA - eng GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - U01 HL100398/HL/NHLBI NIH HHS/United States GR - K01 HL121045/HL/NHLBI NIH HHS/United States GR - 2 UL1 TR000445-06/TR/NCATS NIH HHS/United States GR - K23HL123938/HL/NHLBI NIH HHS/United States GR - UL1 TR001425/TR/NCATS NIH HHS/United States GR - UL1 RR024975/RR/NCRR NIH HHS/United States GR - K23 HL123938/HL/NHLBI NIH HHS/United States GR - UL1 RR024975-01/RR/NCRR NIH HHS/United States GR - K01HL121045/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20151216 PL - United States TA - Pediatr Res JT - Pediatric research JID - 0100714 RN - 0 (Biomarkers) SB - IM MH - Animals MH - Biomarkers/*metabolism MH - Case-Control Studies MH - Cohort Studies MH - Dogs MH - Heart/*physiopathology MH - Humans MH - Muscle, Skeletal/*physiopathology MH - Muscular Dystrophy, Duchenne/genetics/*physiopathology MH - *Oligonucleotide Array Sequence Analysis PMC - PMC4837049 MID - NIHMS727865 EDAT- 2015/12/18 06:00 MHDA- 2017/01/31 06:00 PMCR- 2016/06/16 CRDT- 2015/12/18 06:00 PHST- 2015/06/11 00:00 [received] PHST- 2015/09/28 00:00 [accepted] PHST- 2015/12/18 06:00 [entrez] PHST- 2015/12/18 06:00 [pubmed] PHST- 2017/01/31 06:00 [medline] PHST- 2016/06/16 00:00 [pmc-release] AID - pr2015257 [pii] AID - 10.1038/pr.2015.257 [doi] PST - ppublish SO - Pediatr Res. 2016 Apr;79(4):629-36. doi: 10.1038/pr.2015.257. Epub 2015 Dec 16.