Plasma tumour necrosis factor correlates with mRNA expression of tumour necrosis factor and mitochondrial transcription factors in skeletal muscle in patients with chronic heart failure treated with cardiac resynchronization therapy: potential role in myopathy

Abstract

Chronic heart failure (CHF) is characterized by inflammation and skeletal muscle myopathy, including impaired fibre type distribution and reduced capillary density, reduced cytochrome oxidase activity and reduced mitochondrial density. The myopathy is associated with activation of the interleukin-6–C-reactive protein pathway and the prototypical inflammatory cytokine tumour necrosis factor (TNF) with alterations in the mRNA expression of enzymes essential in mitochondrial biogenesis. Central in this process are peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide adenine dinucleotide and mitochondrial transcription factor (TFAM). The covariance over time between plasma levels of TNF and skeletal muscle mRNA expression of this pro-inflammatory cytokine, and the correlation between TNF and mRNA expression of enzymes essential in mitochondrial biogenesis and skeletal muscle pathology has not previously been evaluated in patients with CHF on stable medical treatment. The methods have been described previously and are briefly presented here.