Chronic obstructive pulmonary disease (COPD) is associated with a high incidence of cardiovascular diseases. Although exercise training (ET) can reverse vascular deficiencies before the onset of an atherosclerotic cardiovascular disease in sedentary healthy subjects (SHS), vascular adaptations to ET, particularly angiogenic processes are blunted in COPD patients.

The aim of this study was to assess peripheral capillaries formation and maturation in COPD patients and determine whether systemic circulating factors could disturb these processes.

Seven SHS and 14 matched COPD patients performed 10 weeks of ET. Functional assessments, vastus lateralis biopsies and blood samples collection were performed before and after 5 and 10 weeks of ET. Analysis of capillary number and maturation, through capillary-to-fiber (C/F) ratio and pericyte coverage (PcCOV) respectively were performed. We also investigated the effect of post-ET serum of COPD patients and SHS on pericyte morphological changes, in human pericyte culture, and on mesenchymal stem cells (MSC) differentiation into pericyte, in a human MSC/Endothelial cell co-culture model. The MSC differentiation was assessed with calponin expression.

In response to ET, we observed an increase of PcCOV only in SHS (Group/Time interaction: P<0.05) leading to lower PcCOV value in COPD patients after ET compare to SHS (P<0.001) and this despite a similar increase of C/F in SHS and COPD patients. The serum of COPD patients induced a greater pericyte elongation than SHS serum (P<0.001). Finally, the Calponin expression in MSC was higher in co-culture exposed to SHS serum compared to these exposed to COPD serum (P<0.001).

This study provides evidences supporting a defective capillary maturation in COPD patients during training-induced angiogenesis. It provides first evidences for a systemic circulating cause in these impairments.