TY - JOUR
T1 - Analysis of skeletal muscle gene expression patterns and the impact of functional capacity in patients with systolic heart failure
AU - Forman, Daniel E.
AU - Daniels, Karla M.
AU - Cahalin, Lawrence P.
AU - Zavin, Alexandra
AU - Allsup, Kelly
AU - Cao, Peirang
AU - Santhanam, Mahalakshmi
AU - Joseph, Jacob
AU - Arena, Ross
AU - Lazzari, Antonio
AU - Schulze, P. Christian
AU - Lecker, Stewart H.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2014/6
Y1 - 2014/6
N2 - Background Declining physical function is common among systolic heart failure (HF) patients and heralds poor clinical outcomes. We hypothesized that coordinated shifts in expression of ubiquitin-mediated atrophy-promoting genes are associated with muscle atrophy and contribute to decreased physical function. Methods Systolic HF patients (left ventricular ejection fraction [LVEF] ≠40%) underwent skeletal muscle biopsies (nondominant vastus lateralis) and comprehensive physical assessments. Skeletal muscle gene expression was assessed with the use of real-time polymerase chain reaction. Aerobic function was assessed with the use of cardiopulmonary exercise and 6-minute walk tests. Strength capacity was assessed with the use of pneumatic leg press (maximum strength and power). Serologic inflammatory markers also were assessed. Results 54 male patients (66.6 ;plusmn; 10.0 years) were studied: 24 systolic HF patients (mean LVEF 28.9 ;plusmn; 7.8%) and 30 age-matched control subjects. Aerobic and strength parameters were diminished in HF versus control. FoxO1 and FoxO3 were increased in HF versus control (7.9 ;plusmn; 6.2 vs 5.0 ;plusmn; 3.5, 6.5 ;plusmn; 4.3 vs 4.3 ;plusmn; 2.8 relative units, respectively; P ≠;.05 in both). However, atrogin-1 and MuRF-1 were similar in both groups. PGC-1α was also increased in HF (7.9 ± 5.4 vs. 5.3 ± 3.6 relative units; P <.05). Muscle levels of insulin-like growth factor (IGF) 1 as well as serum levels of tumor necrosis factor α, C-reactive protein, interleukin (IL) 1β, and IL-6 were similar in HF and control. Conclusion Expression of the atrophy-promoting genes FoxO1 and FoxO3 were increased in skeletal muscle in systolic HF compared with control, but other atrophy gene expression patterns (atrogin-1 and MuRF-1), as well as growth promoting patterns (IGF-1), were similar. PGC-1α, a gene critical in enhancing mitochondrial function and moderating FoxO activity, may play an important counterregulatory role to offset ubiquitin pathway-mediated functional decrements.
AB - Background Declining physical function is common among systolic heart failure (HF) patients and heralds poor clinical outcomes. We hypothesized that coordinated shifts in expression of ubiquitin-mediated atrophy-promoting genes are associated with muscle atrophy and contribute to decreased physical function. Methods Systolic HF patients (left ventricular ejection fraction [LVEF] ≠40%) underwent skeletal muscle biopsies (nondominant vastus lateralis) and comprehensive physical assessments. Skeletal muscle gene expression was assessed with the use of real-time polymerase chain reaction. Aerobic function was assessed with the use of cardiopulmonary exercise and 6-minute walk tests. Strength capacity was assessed with the use of pneumatic leg press (maximum strength and power). Serologic inflammatory markers also were assessed. Results 54 male patients (66.6 ;plusmn; 10.0 years) were studied: 24 systolic HF patients (mean LVEF 28.9 ;plusmn; 7.8%) and 30 age-matched control subjects. Aerobic and strength parameters were diminished in HF versus control. FoxO1 and FoxO3 were increased in HF versus control (7.9 ;plusmn; 6.2 vs 5.0 ;plusmn; 3.5, 6.5 ;plusmn; 4.3 vs 4.3 ;plusmn; 2.8 relative units, respectively; P ≠;.05 in both). However, atrogin-1 and MuRF-1 were similar in both groups. PGC-1α was also increased in HF (7.9 ± 5.4 vs. 5.3 ± 3.6 relative units; P <.05). Muscle levels of insulin-like growth factor (IGF) 1 as well as serum levels of tumor necrosis factor α, C-reactive protein, interleukin (IL) 1β, and IL-6 were similar in HF and control. Conclusion Expression of the atrophy-promoting genes FoxO1 and FoxO3 were increased in skeletal muscle in systolic HF compared with control, but other atrophy gene expression patterns (atrogin-1 and MuRF-1), as well as growth promoting patterns (IGF-1), were similar. PGC-1α, a gene critical in enhancing mitochondrial function and moderating FoxO activity, may play an important counterregulatory role to offset ubiquitin pathway-mediated functional decrements.
KW - gene expression
KW - Heart failure
KW - skeletal muscle
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U2 - 10.1016/j.cardfail.2014.03.007
DO - 10.1016/j.cardfail.2014.03.007
M3 - Article
C2 - 24704539
AN - SCOPUS:84901720013
VL - 20
SP - 422
EP - 430
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
SN - 1071-9164
IS - 6
ER -