Quadriceps muscle weakness and atrophy are associated with a differential Epigenetic Profile in Advanced COPD

Epigenetic mechanisms regulate muscle mass and function in models of muscle dysfunction and atrophy. We assessed whether quadriceps muscle weakness and atrophy are associated with a differential expression profile of epigenetic events in patients with advanced COPD. In vastus lateralis (VL) of sedentary severe COPD patients (n=41), who were further subdivided into those with (n=25) and without (n=16) muscle weakness, and healthy controls (n=19), expression of muscle-enriched microRNAs, histone acetyltransferases (HATs) and deacetylases (HDACs), growth and atrophy signaling markers, total protein and histone acetylation, transcription factors, small ubiquitin-related modifier (SUMO) ligases, and muscle structure were explored. All subjects were clinically evaluated. Compared to controls, in VL of all COPD together and in muscle-weakness patients, expression of miR-1, -206, and -27a, levels of lysine-acetylated proteins and histones, and acetylated histone 3 were increased, while expression of HDAC3, HDAC4, sirtuin-1, IGF-1 were decreased, Akt expression did not differ, follistatin expression was greater, whereas myostatin expression was lower, serum reponse factor (SRF) expression was increased, and fiber size of fast-twitch fibers was significantly reduced. In VL of severe COPD patients with muscle weakness and atrophy, epigenetic events regulate muscle differentiation rather than proliferation, and muscle growth and atrophy signaling, probably as feedback mechanisms to preve...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research