DIFFERENCES IN MICRORNA EXPRESSION PROFILE BETWEEN VASTUS LATERALIS SAMPLES AND MYOTUBES IN COPD CACHEXIA.

Quadriceps muscle weakness and wasting are common comorbidities in COPD. MicroRNA expression upregulation may favor muscle mass growth and differentiation. We hypothesized whether the profile of muscle-enriched microRNAs in cultured myotubes differs between COPD patients of a wide range of body composition and healthy controls and whether expression levels of those microRNAs from COPD and controls differ between in vivo and in vitro conditions. Twenty-nine COPD patients (n=15 with muscle wasting, FFMI 15 kg/m2 and n=14 with normal body composition, FFMI 18 kg/m2 ) and 10 healthy controls (FFMI, 19 kg/m2 ) were consecutively recruited. Biopsies from the vastus lateralis were obtained in all study subjects. A fragment of each biopsy was used to obtain primary cultures, in which muscle cells were first proliferated to be then differentiated into actual myotubes. In both sets of experiments (in vivo biopsies and in vitro myotubes) the following muscle-enriched microRNAs were analyzed using qRT-PCR: miR-1, miR-133, miR-206, miR-486, miR-29a, miR-27a, and miR-181a from all the study subjects. While the expression of miR-1, miR-206, miR-486, and miR-29a was upregulated in the muscle biopsies of COPD patients compared to those of healthy controls, levels of all the study microRNAs in the myotubes (primary cultured cells) did not significantly differ between COPD patients and the controls. We conclude from these findings that environmental factors (blood flow, muscle metabolism, inflammation) taking place in vivo (biopsies) in muscles may account for the differences observed in microRNA expression between COPD patients and controls. In the myotubes, however, the expression of the same microRNAs did not differ between the study subjects as such environmental factors were not present. These findings suggest that therapeutic strategies should rather target environmental factors in COPD muscle wasting as the profile of microRNA expression in myotubes was similar in patients to that observed in the healthy controls.