PMID- 23953820
OWN - NLM
STAT- MEDLINE
DCOM- 20140403
LR  - 20211021
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Print)
IS  - 1053-2498 (Linking)
VI  - 32
IP  - 9
DP  - 2013 Sep
TI  - Modifications of skeletal muscle ryanodine receptor type 1 and exercise 
      intolerance in heart failure.
PG  - 925-9
LID - S1053-2498(13)01339-9 [pii]
LID - 10.1016/j.healun.2013.06.026 [doi]
AB  - BACKGROUND: In experimental heart failure animal models, remodeling of skeletal 
      and cardiac muscle ryanodine receptors (RyR), including phosphorylation, 
      S-nitrosylation and oxidation, have been reported to contribute to pathologic 
      Ca2+ release, impaired muscle function and fatigue. However, it is not known 
      whether similar remodeling of RyR1 in skeletal muscle occurs in patients with 
      heart failure, and if this is associated with impairment of physical activity. 
      METHODS: We studied 8 sedentary patients with New York Heart Association (NYHA) 
      Class III heart failure and 7 age-matched, healthy, but sedentary controls. All 
      heart failure patients had NYHA Class III and peak VO2, echocardiography and 
      NT-proBNP data consistent with moderate to severe heart failure. The age-matched 
      controls included were allowed hypertension but sub-clinical heart failure was to 
      have been ruled out by normal peak VO2, echocardiography and NT-proBNP. RESULTS: 
      Exercise capacity (VO2max) differed by almost 2-fold between heart failure 
      patients and age-matched controls. Compared with controls, skeletal muscle RyR1 
      in heart failure patients was excessively phosphorylated, S-nitrosylated and 
      oxidized. Furthermore, RyR1 from heart failure patients was depleted of its 
      stabilizing protein FK 506-binding protein 12 (FKBP12, or calstabin1). 
      CONCLUSIONS: For the first time we show that skeletal muscle RyR1 from human 
      heart failure is post-translationally modified, which corroborates previous data 
      from experimental animal studies. This indicates pathologic Ca2+ release as a 
      potential mechanism behind skeletal muscle weakness and impaired exercise 
      tolerance in patients with heart failure and suggests a potential target for 
      pharmacologic intervention.
CI  - Copyright (c) 2013 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Rullman, Eric
AU  - Rullman E
AD  - Department of Cardiology, Karolinska University Hospital, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Andersson, Daniel C
AU  - Andersson DC
FAU - Melin, Michael
AU  - Melin M
FAU - Reiken, Steven
AU  - Reiken S
FAU - Mancini, Donna M
AU  - Mancini DM
FAU - Marks, Andrew R
AU  - Marks AR
FAU - Lund, Lars H
AU  - Lund LH
FAU - Gustafsson, Thomas
AU  - Gustafsson T
LA  - eng
GR  - R01 AI039794/AI/NIAID NIH HHS/United States
GR  - R01 HL061503/HL/NHLBI NIH HHS/United States
GR  - R01 AR060037/AR/NIAMS NIH HHS/United States
GR  - R01HL056180/HL/NHLBI NIH HHS/United States
GR  - R01HL061503/HL/NHLBI NIH HHS/United States
GR  - R01 HL056180/HL/NHLBI NIH HHS/United States
GR  - P01 HL067849/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Peptide Fragments)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - 0 (pro-brain natriuretic peptide (1-76))
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
SB  - IM
MH  - Aged
MH  - Biopsy
MH  - Case-Control Studies
MH  - Comorbidity
MH  - Echocardiography
MH  - Exercise Tolerance/*physiology
MH  - Female
MH  - Heart Failure/epidemiology/*metabolism/*physiopathology
MH  - Humans
MH  - Hypertension/epidemiology/metabolism/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Muscle, Skeletal/*metabolism/pathology
MH  - Natriuretic Peptide, Brain/metabolism
MH  - Oxygen Consumption/physiology
MH  - Peptide Fragments/metabolism
MH  - Ryanodine Receptor Calcium Release Channel/*metabolism
MH  - Severity of Illness Index
PMC - PMC4399850
MID - NIHMS678895
OTO - NOTNLM
OT  - ageing
OT  - muscle fatigue activity
OT  - physical exercise capacity calcium oxidative stress
OT  - post-translational contraction
OT  - protein processing
EDAT- 2013/08/21 06:00
MHDA- 2014/04/04 06:00
PMCR- 2015/04/16
CRDT- 2013/08/20 06:00
PHST- 2013/01/25 00:00 [received]
PHST- 2013/06/26 00:00 [revised]
PHST- 2013/06/28 00:00 [accepted]
PHST- 2013/08/20 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/04/04 06:00 [medline]
PHST- 2015/04/16 00:00 [pmc-release]
AID - S1053-2498(13)01339-9 [pii]
AID - 10.1016/j.healun.2013.06.026 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2013 Sep;32(9):925-9. doi: 10.1016/j.healun.2013.06.026.