Kritikaki Efpraxia, Terzis Gerasimos, Soundararajan Meera, Vogiatzis Ioannis, Simoes Davina C M
Faculty of Health and Life Sciences, Northumbria University Newcastle, Newcastle upon Tyne, UK.
Sports Performance Laboratory, School of Physical Education and Sports Science, National and Kapodistrian University of Athens, Athens, Greece.
ERJ Open Res. 2025 Jan 20;11(1). doi: 10.1183/23120541.00543-2024. eCollection 2025 Jan.
In response to exercise-based pulmonary rehabilitation (PR), the type of muscle fibre remodelling differs between COPD patients with peripheral muscle wasting (atrophic patients with COPD) and those without wasting (nonatrophic patients with COPD). Extracellular matrix (ECM) proteins are major constituents of the cell micro-environment steering cell behaviour and regeneration. We investigated whether the composition of ECM in atrophic compared to nonatrophic patients with COPD differs in response to PR.
Vastus lateralis muscle biopsies from 29 male COPD patients (mean±sem forced expiratory volume in 1 s: 43±6% predicted) classified according to their fat-free mass index as atrophic (<17 kg·m, n=10) or nonatrophic (≥17 kg·m, n=19) were analysed before and after a 10-week PR programme for myofibre distribution and size, whereas a selection of ECM molecules was quantified using ELISA and real-time PCR.
In nonatrophic patients with COPD PR was associated with increased myofibre type I distribution (by 6.6±2.3%) and cross-sectional area (CSA) (by 16.4±4.8%), whereas in atrophic patients with COPD, PR induced increased myofibre type IIa distribution (by 9.6±2.8%) and CSA (by 12.1±3.2%). PR induced diverse intramuscular ECM adaptations in atrophic compared to nonatrophic patients with COPD. Accordingly, following PR there was a significant increase in protein levels of ECM biomarkers (collagen type I by 90 pg·mL; collagen type IV by 120 pg·mL; decorin by 70 pg·mL) only in nonatrophic patients with COPD. Conversely, post-PR, osteopontin, a protein known for its dystrophic effects, and tenacin C, a necroptosis compensatory factor facilitating muscle regeneration, were upregulated at protein levels (by 280 pg·mLand 40 pg·mL, respectively) in atrophic patients with COPD, whereas fibronectin protein levels were decreased.
These findings suggest that the differential PR-induced myofibre adaptations in atrophic compared to nonatrophic patients with COPD could be associated with inadequate remodelling of the intramuscular ECM environment.
针对基于运动的肺康复（PR），慢性阻塞性肺疾病（COPD）合并外周肌肉萎缩患者（萎缩型COPD患者）与未合并肌肉萎缩患者（非萎缩型COPD患者）的肌纤维重塑类型有所不同。细胞外基质（ECM）蛋白是调控细胞行为和再生的细胞微环境的主要组成部分。我们研究了与非萎缩型COPD患者相比，萎缩型COPD患者的ECM组成在PR治疗后的差异。
对29例男性COPD患者（1秒用力呼气容积均值±标准误：占预计值的43±6%）进行了股外侧肌活检，根据其去脂体重指数分为萎缩型（<17 kg·m²，n = 10）或非萎缩型（≥17 kg·m²，n = 19）。在为期10周的PR方案前后，分析肌纤维分布和大小，同时使用酶联免疫吸附测定（ELISA）和实时聚合酶链反应（PCR）对一系列ECM分子进行定量分析。
在非萎缩型COPD患者中，PR与I型肌纤维分布增加（增加6.6±2.3%）和横截面积（CSA）增加（增加16.4±4.8%）相关；而在萎缩型COPD患者中，PR导致IIa型肌纤维分布增加（增加9.6±2.8%）和CSA增加（增加12.1±3.2%）。与非萎缩型COPD患者相比，PR在萎缩型COPD患者中诱导了不同的肌内ECM适应性变化。因此，PR治疗后，仅在非萎缩型COPD患者中，ECM生物标志物的蛋白水平显著升高（I型胶原增加90 pg·mL；IV型胶原增加120 pg·mL；核心蛋白聚糖增加70 pg·mL）。相反，在萎缩型COPD患者中，PR治疗后，具有营养不良作用的骨桥蛋白和促进肌肉再生的坏死性凋亡补偿因子肌腱蛋白C的蛋白水平上调（分别增加280 pg·mL和40 pg·mL），而纤连蛋白蛋白水平降低。
这些发现表明，与非萎缩型COPD患者相比，PR在萎缩型COPD患者中诱导的肌纤维适应性差异可能与肌内ECM环境重塑不足有关。
