Muscle weakness and wasting are common in patients with chronic obstructive pulmonary disease (COPD). Myostatin regulatory pathway is involved in muscle mass maintenance. Whether the expression of markers of the myostatin pathway is altered in the lower limb muscles of sarcopenic COPD patients remains to be fully elucidated.  We sought to characterize gene and protein expression profile of the myostatin pathway and its downstream targets in COPD sarcopenia. In the vastus lateralis (VL) samples of 41 severe COPD patients (23 sarcopenic and 18 non-sarcopenic) and 14 healthy controls, mRNA expression levels of myostatin, activin A, activin receptors (ACVR2Aa and ACVR2B), SMAD2, SMAD3, SMAD4, AKT1, PI3KR1, IGF1 and follistatin were quantified using qRT?PCR, and those of myostatin, SMAD2/p-SMAD2, SMAD3/p-SMAD3 and SMAD4 protein levels were measured by immunoblotting. In sarcopenic COPD patients, nutritional and muscle function status were reduced compared to non-sarcopenic and healthy controls. In muscle specimens of sarcopenic COPD, mRNA levels of myostatin, IGF1, and follistatin were greater, while those of activin A and SMAD3 were lower than in the controls and non-sarcopenic patients. Protein levels of myostatin, p-SMAD2, p-SMAD3 and SMAD4 significantly increased in sarcopenic patients compared to control subjects. The lower limb muscles of sarcopenic COPD patients exhibited an upregulation of the myostatin pathway, whereas activin was downregulated. Accelerated myostatin activity underlies sarcopenia and muscle weakness in severe COPD that should be targeted therapeutically.

Funding: FIS 18/00075, FIS 21/00215 (FEDER, ISC-III), Intensificación INT19, CIBERES (ISC-III), SEPAR-2020