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

Abstract

Rationale: Improvements in skeletal muscle endurance and oxygen uptake are blunted in COPD patients, 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 weeks of exercise training in COPD patients and sedentary healthy subjects (SHS). Methods: Fourteen COPD patients were compared to seven matched SHS. SHS trained at moderate intensity corresponding to their first ventilatory threshold. COPD patients trained at the same relative (%V'O2: COPD-RI) or absolute (ml/min/kg: COPD-AI) intensity as SHS. Capillary-to-fiber ratio (C/F) and pericyte coverage were assessed from vastus lateralis muscle biopsies, before and after 5 and 10 weeks 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. Results: SHS showed greater improvement in aerobic capacity (V'O2VT) than both COPD-RI and COPD-AI patients (GroupxTime: p=0.004). Despite a preserved increase in the C/F ratio, pericyte coverage did not increase in COPD patients in response to training, contrary to SHS (GroupxTime: 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). Conclusions: Both functional capacities and pericyte coverage responses to exercise training are blunted in COPD patients. We also provide direct evidence of the deleterious effect of COPD circulating factors on pericyte morphology and differentiation.

Cellular interplay in skeletal muscle regeneration and wasting: insights from animal models

“…We have also observed evidences of an impairment of the capillary maturation, with disturbed pericyte/endothelial interactions during exercise training 93 . In contrast with healthy sedentary subjects, the pericyte coverage of muscle capillaries in COPD patients during exercise training has been found defective 94 . This capillary maturation impairment occurs early in the disease time course, as a consequence of deleterious muscle micro‐environment 94 …”

“…93 In contrast with healthy sedentary subjects, the pericyte coverage of muscle capillaries in COPD patients during exercise training has been found defective. 94 This capillary maturation impairment occurs early in the disease time course, as a consequence of deleterious muscle micro-environment. 94 Concerning progenitor cells, it has been shown that SCs exhibit alterations of their own in COPD muscle, notably a senescent phenotype and increased oxidative stress, although their density seems unchanged.…”

“…94 This capillary maturation impairment occurs early in the disease time course, as a consequence of deleterious muscle micro-environment. 94 Concerning progenitor cells, it has been shown that SCs exhibit alterations of their own in COPD muscle, notably a senescent phenotype and increased oxidative stress, although their density seems unchanged. 95,96 Furthermore, primary SCs isolated from COPD patients displayed a delayed activation in culture, a decreased expression of myosin heavy chain during myotube formation 97 and a reduced myotube diameter 95 compared with controls, pointing towards impaired differentiation.…”

“… 93 In contrast with healthy sedentary subjects, the pericyte coverage of muscle capillaries in COPD patients during exercise training has been found defective. 94 This capillary maturation impairment occurs early in the disease time course, as a consequence of deleterious muscle micro‐environment. 94 …”

Response to Electrostimulation Is Impaired in Muscle Cells from Patients with Chronic Obstructive Pulmonary Disease

“…Sedentary healthy subjects and stable patients with COPD were recruited in previous studies with no link to the present study [ 18 , 20 , 21 ]. The institutional ethics committees of the Montpellier University Hospital (Comité de Protection des Personnes Sud Méditerranée IV 2008-03-ESSS-V2, 2009-04-BPCO-V2, 2011-A00842-39 and 2013-A01199-36) approved the studies.…”