Patients with advanced chronic heart failure (CHF) are characterized by progressive muscle wasting. The two E3-ligases Rnf28 and Atrogin-1 controlling the activation of the ubiquitinproteasome system might be of importance for the regulation of muscle size. Given the convincing effect of regular physical exercise training (ET) in CHF, it was the aim of the present trial to elucidate, whether ET affects both mentioned enzymes in CHF and whether this is associated with an increase in skeletal muscle mass. METHODS: 37 patients with severe CHF were randomized to 12 weeks of ET or sedentary lifestyle (control). The expression of Rnf28 and Atrogin-1 in the skeletal muscle was analyzed by RT-PCR and Western blotting. Skeletal muscle cross sectional area (CSA) was measured by computed tomography. RESULTS: In CHF patients ET led to a significant reduction in skeletal muscle mRNA transcription (from 14.3 +/- 2.0 to 8.7 +/- 1.4 arbitrary units; p < 0.05 versus baseline and versus control for the change) and protein expression of Rnf28 (from 4.70 +/- 1.35 to 2.84 +/- 0.65 arbitrary units; p < 0.05 versus baseline and versus control for the change). This was accompanied by a significant increase in total muscle CSA of both thighs (from 139.9 +/- 5.2 to 149.2 +/- 5.9 cm2; p < 0.05 versus baseline and versus control for the change). On the contrary, Atrogin-1 was not affected. CONCLUSION: In patients with advanced CHF, regular physical exercise training led to a decrease in Rnf28 expression in the skeletal muscle. This was linked to an increase in skeletal muscle cross sectional area, supporting the notion that ET has anti-catabolic properties in CHF.

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