COPD is deleterious for pericytes: implications during training-induced angiogenesis in skeletal muscle.

ABSTRACT

Improvements in skeletal muscle endurance and oxygen uptake are blunted in patients with chronic obstructive pulmonary disease (COPD), possibly because of a limitation in the muscle capillary oxygen supply. Pericytes are critical for capillary blood flow adaptation during angiogenesis but may be impaired by COPD systemic effects, which are mediated by circulating factors. This study compared the pericyte coverage of muscle capillaries in response to 10 wk of exercise training in patients with COPD and sedentary healthy subjects (SHS). Fourteen patients with COPD were compared with seven matched SHS. SHS trained at moderate intensity corresponding to an individualized moderate-intensity patient with COPD trained at the same relative (%V̇o2 COPD-RI) or absolute (mL·min-1·kg-1 COPD-AI) intensity as SHS. Capillary-to-fiber ratio (C/F) and NG2+ pericyte coverage were assessed from vastus lateralis muscle biopsies, before and after 5 and 10 wk of training. We also tested in vitro the effect of COPD and SHS serum on pericyte morphology and mesenchymal stem cell (MSC) differentiation into pericytes. SHS showed greater improvement in aerobic capacity (V̇o2VT) than both patients with COPD-RI and patients with COPD-AI (Group × Time P = 0.004). Despite a preserved increase in the C/F ratio, NG2+ pericyte coverage did not increase in patients with COPD in response to training, contrary to SHS (Group × Time P = 0.011). Conversely to SHS serum, COPD serum altered pericyte morphology (P < 0.001) and drastically reduced MSC differentiation into pericytes (P < 0.001). Both functional capacities and pericyte coverage responses to exercise training are blunted in patients with COPD. We also provide direct evidence of the deleterious effect of COPD circulating factors on pericyte morphology and differentiation.NEW & NOTEWORTHY This work confirms the previously reported impairment in the functional response to exercise training of patients with COPD compared with SHS. Moreover, it shows for the first time that pericyte coverage of the skeletal capillaries is drastically reduced in patients with COPD compared with SHS during training-induced angiogenesis. Finally, it provides experimental evidence that circulating factors are involved in the impaired pericyte coverage of patients with COPD.