Impaired anabolic signaling may explain skeletal muscle wasting in CHF
MedWire News: Skeletal muscle wasting that is often seen in patients with chronic heart failure (CHF) may be partly explained by a reduction in anabolic signaling rather than simply physical inactivity, research indicates.
The findings showed that the biomarker Akt was reduced in CHF patients relative to sedentary individuals without CHF - a finding that was linked to decreased skeletal muscle myosin protein content and knee extensor isometric torque.
"We are confident that our results reflect the unique effects of the HF syndrome, rather than muscle disuse, atrophy, end-stage disease, or acute illness," said Michael Toth (University of Vermont, Burlington, USA) in the Journal of Applied Physiology.
Patients with CHF often experience muscle atrophy and weakness during the course of the disease, which may contribute to their physical disability.
Previous studies have found that CHF patients show a reduction in insulin-like growth factor (IGF)-1 - which is believed to be a key regulator of protein metabolism, stimulating anabolic and inhibiting catabolic pathways.
However, muscle use positively regulates skeletal muscle IGF-1 expression, thus "it is unclear whether diminished local IGF-1 expression observed in prior studies is due to HF or is a consequence of muscle disuse that accompanies the disease," Toth et al comment.
For the current study, therefore, the researchers decided to focus on signaling biomarkers downstream of IGF-1 that have a direct impact on muscle tissue.
In order to limit the confounding effects of muscle disuse and/or acute disease exacerbation they recruited 11 sedentary controls with similar physical activity levels as 11 CHF patients who had not had any bouts of disease exacerbation/hospitalization in the past 6 months.
Patients with CHF showed a significantly lower peak volume of oxygen (VO2) relative to controls (13.7 vs 23.4 ml/kg/min) and a trend for decreased knee extensor isometric torque (129 vs 159 N/m).
IGF-1 expression in skeletal muscle was similar in the two groups. Despite this, CHF patients showed a significant 43% reduction in phosphorylation of Akt at Ser473, compared with controls, whereas there was no significant difference in total Akt protein expression (pAkt/Akt).
Among the patients, reduced pAkt/Akt levels and phospho-mTOR/mTOR correlated with decreased skeletal muscle myosin protein content and knee extensor isometric torque.
Commenting on the study in an accompanying editorial Kyle Timmerman and Blake Rasmussen from the University of Texas Medical Branch, Galveston, said that "uncovering the mechanisms underlying the development of cardiac cachexia is an important area of future research."
They add: "The study by Toth et al represents an important first step toward identifying the cellular mechanisms that may contribute to, or serve as molecular biomarkers for the onset of this condition."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Andrew Czyzewski