Muscle fibre satellite cells are located at a greater distance from capillaries in patients with COPD compared with healthy controls

Abstract

Background: COPD is a disease characterised by skeletal muscle dysfunction. A spatial relationship exists between satellite cells and muscle fibre capillaries, which has been suggested to be of major importance for satellite cell function. In the present study we compared the spatial relationship between satellite cells and capillaries in patients with COPD and age-matched healthy older adults.

Methods: Muscle biopsies were obtained from the vastus lateralis of n=18 patients with COPD (8 female, 10 male; age 66±5 years, mild-to-severe airflow obstruction) and n=18 age-, sex- and body mass index-matched healthy control adults (8 female, 10 male; age 68±5 years). Immunohistochemistry was used to assess type I/II muscle fibre size, distribution, myonuclear content, satellite cell number and fibre capillarisation. In addition, type I/II muscle fibre satellite cell distance to its nearest capillary was assessed.

Results: The percentage of type II muscle fibres was significantly greater in patients with COPD (62±10%) compared with controls (50±12%, p<0.05). Muscle fibre capillarisation was significantly lower in patients with COPD compared with controls (p<0.05). While satellite cell content was not different between groups, type I and type II satellite cell distance to its nearest capillary was significantly greater in patients with COPD (type I: 21.3±4.8 µm; type II: 26.7±9.3 µm) compared with controls (type I: 16.1±3.5 µm; type II: 22.7±5.8 µm; p<0.05).

Conclusion: Satellite cells are located at a greater distance from their nearest capillary in patients with COPD compared with age-matched controls. This increased distance could play a role in impaired satellite cell function in patients with COPD.

FIGURE 1

Representative images for assessment of type I and type II skeletal muscle fibre distribution, fibre size, myonuclear content and capillarisation in a) patients with COPD and b) healthy older adults. Myosin heavy chain (MHC)-I (green) plus laminin (white) plus 4′,6-diamidino-2-phenylindole (DAPI) (blue) plus CD31 (red) staining. Type I and type II c) muscle fibre size and d) capillary-to-fibre ratio. Data are presented as mean±sd, as well as individual data points.

FIGURE 2

Representative images for assessment of type I and type II skeletal muscle satellite cell content and satellite cell distance to its nearest capillary in a,c,e,g) patients with COPD and b,d,f,h) age-matched controls. a,b) Myosin heavy chain (MHC)-I (white) plus laminin (white) plus 4′,6-diamidino-2-phenylindole (DAPI) (blue) plus Pax7 (green) plus CD31 (red) staining. c,d) MHC-I, laminin and DAPI. e,f) CD31 and Pax7. g,h) Pax7 only. Yellow line indicates the measurement of satellite cell distance to its nearest capillary. *: satellite cell.

FIGURE 3

Type I and type II muscle fibre satellite cell a) content and b) distance to nearest capillary in patients with COPD and age-matched healthy controls. Data are presented as mean±sd, as well as individual data points.