PMID- 23204842
OWN - NLM
STAT- MEDLINE
DCOM- 20130515
LR  - 20211021
IS  - 1178-1998 (Electronic)
IS  - 1176-9092 (Print)
IS  - 1176-9092 (Linking)
VI  - 7
DP  - 2012
TI  - Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA 
      Class II heart failure patients.
PG  - 489-97
LID - 10.2147/CIA.S37879 [doi]
AB  - BACKGROUND: Heart failure (HF), a debilitating disease in a growing number of 
      adults, exerts structural and neurohormonal changes in both cardiac and skeletal 
      muscles. However, these alterations and their affected molecular pathways remain 
      uncharacterized. Disease progression is known to transform skeletal muscle fiber 
      composition by unknown mechanisms. In addition, perturbation of specific hormonal 
      pathways, including those involving skeletal muscle insulin-like growth factor-1 
      (IGF-1) and insulin-like growth factor-binding protein-5 (IGFB-5) appears to 
      occur, likely affecting muscle metabolism and regeneration. We hypothesized that 
      changes in IGF-1 and IGFB-5 mRNA levels correlate with the transformation of 
      single-skeletal muscle fiber myosin heavy chain isoforms early in disease 
      progression, making these molecules valuable markers of skeletal muscle changes 
      in heart failure. MATERIALS AND METHODS: To investigate these molecules during 
      "early" events in HF patients, we obtained skeletal muscle biopsies from New York 
      Heart Association (NYHA) Class II HF patients and controls for molecular analyses 
      of single fibers, and we also quantified isometric strength and muscle size. 
      RESULTS: There were more (P < 0.05) single muscle fibers coexpressing two or more 
      myosin heavy chains in the HF patients (30% +/- 7%) compared to the control 
      subjects (13% +/- 2%). IGF-1 and IGFBP-5 expression was fivefold and 15-fold lower 
      in patients with in HF compared to control subjects (P < 0.05), respectively. 
      Strikingly, there was a correlation in IGF-1 expression and muscle 
      cross-sectional area (P < 0.05) resulting in a decrease in whole-muscle quality 
      (P < 0.05) in the HF patients, despite no significant decrease in isometric 
      strength or whole-muscle size. CONCLUSION: These data indicate that molecular 
      alterations in myosin heavy chain isoforms, IGF-1, and IGFB-5 levels precede the 
      gross morphological and functional deficits that have previously been associated 
      with HF, and may be used as a predictor of functional outcome in patients.
FAU - Godard, Michael P
AU  - Godard MP
AD  - Department of Nutrition and Kinesiology, University of Central Missouri, 
      Warrensburg, MO 64093, USA. godard@ucmo.edu
FAU - Whitman, Samantha A
AU  - Whitman SA
FAU - Song, Yao-Hua
AU  - Song YH
FAU - Delafontaine, Patrice
AU  - Delafontaine P
LA  - eng
GR  - R01 HL080682/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20121112
PL  - New Zealand
TA  - Clin Interv Aging
JT  - Clinical interventions in aging
JID - 101273480
RN  - 0 (Insulin-Like Growth Factor Binding Protein 5)
RN  - 0 (RNA, Messenger)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
MH  - Aged
MH  - Biopsy, Needle
MH  - Exercise
MH  - Female
MH  - Heart/*physiopathology
MH  - Heart Failure/*physiopathology
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 5/genetics/*metabolism
MH  - Insulin-Like Growth Factor I/genetics/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Muscle Strength
MH  - Muscle, Skeletal/*physiopathology
MH  - Myosin Heavy Chains/metabolism
MH  - RNA, Messenger/biosynthesis
PMC - PMC3508558
OTO - NOTNLM
OT  - IGF1 and IGFBP-5
OT  - hybrid fibers
OT  - muscle quality
EDAT- 2012/12/04 06:00
MHDA- 2013/05/17 06:00
PMCR- 2012/11/12
CRDT- 2012/12/04 06:00
PHST- 2012/12/04 06:00 [entrez]
PHST- 2012/12/04 06:00 [pubmed]
PHST- 2013/05/17 06:00 [medline]
PHST- 2012/11/12 00:00 [pmc-release]
AID - cia-7-489 [pii]
AID - 10.2147/CIA.S37879 [doi]
PST - ppublish
SO  - Clin Interv Aging. 2012;7:489-97. doi: 10.2147/CIA.S37879. Epub 2012 Nov 12.