Altered metabolic activity and redox balance are associated with a proliferative phenotype in COPD airway smooth muscle cells.

Background: Oxidative stress in COPD airways causes mitochondrial dysfunction and remodelling, which entails airway smooth muscle (ASM) layer thickening. The latter results from ASM cell (ASMC) proliferation driven by mediators such as transforming growth factor (TGF)-β. Cellular metabolism, ATP levels and reactive oxygen species (ROS) are key determinants of cell proliferation. Aims a Objectives: To determine whether changes in energy metabolism and redox balance in COPD ASMCs contribute to their proliferative phenotype. Methods: ASMCs were cultured from resected airways of healthy ex-smokers and COPD patients (n=7/group) and stimulated with TGF-β (1ng/ml) and FBS (2.5%; TGF-β/FBS). Proliferation was determined by cell counting, intracellular ROS levels by dichlorofluorescein staining and ATP production rate using a Seahorse XFp analyser. Glycolysis was inhibited using the compounds 2-deoxy-D-glucose (2-DG) and dichloroacetic acid (DCA). Results: At baseline, COPD ASMCs showed a lower ATP production rate (28%; p Conclusion: Altered metabolic and redox activity are associated with a proliferative phenotype in COPD ASMCs.