Abstract
BACKGROUND: Sarcopenia, defined as the loss of muscle mass and function, represents one of the most relevant comorbidities in patients with COPD even at early stages. We hypothesised that sarcopenia defines a specific clinical phenotype in COPD irrespective of respiratory disease severity. Markers of myostatin/Smad2/Smad3 and IGF-1/PI3K/Akt may be differentially expressed in the vastus lateralis (VL) of patients with COPD-associated sarcopenia. METHODS: In muscle specimens from VL, markers of the myostatin/Smad2/Smad3, Smad4 and IGF-1/PI3K/Akt pathways were evaluated (real-time PCR and immunoblotting) and correlations between clinical and biological variables of patients with sarcopenia (n=23), without sarcopenia (n=18) and healthy controls (n=13) were examined. RESULTS: In the VL of sarcopenic COPD patients, expression levels of myostatin, Smad2/Smad3 and Smad4 increased compared with those in nonsarcopenic patients and healthy controls. In sarcopenic limb muscles of patients with COPD, the myostatin Smad2/Smad3 pathway was differentially activated from patients without sarcopenia and healthy controls. Among sarcopenic patients, myostatin and p-Smad3/Smad3 levels negatively correlated with fat-free mass index (r=-0.727, p=0.026 and r=-0.703, p=0.035, respectively), myostatin and Smad4 levels correlated with quadriceps strength (r=-0.886, p=0.003 and r=-0.431, p=0.040, respectively) and myostatin correlated with diffusion capacity (r=-0.781, p=0.022). Remarkable negative correlations were observed between clinical parameters related to body composition and quadriceps muscle strength and levels of the myostatin Smad2/Smad3 pathway, suggesting its implication in the process of muscle atrophy in COPD. IGF1 gene expression was also upregulated in the VL of sarcopenic patients. CONCLUSION: Collectively, these findings offer a potential therapeutic target in COPD-associated sarcopenia.