Crucial role of fatty acid oxidation in asthmatic bronchial smooth muscle remodelling

Background Bronchial smooth muscle (BSM) remodelling in asthma is related to an increased mitochondrial biogenesis and enhanced BSM cell proliferation asthma. Since mitochondria produce the highest levels of cellular energy fatty acid β-oxidation most powerful way ATP, we hypothesised that, asthmatic cells, energetic metabolism shifted towards acids. Objectives We aimed characterise both vitro ex vivo identify a novel target for reducing proliferation. Methods 21 31 non-asthmatic patients were enrolled. used metabolomic proteomic approaches study cells. Oxidative stress, ATP synthesis, endocytosis, metabolite production, metabolic capabilities, networks, apoptosis assessed on Fatty content was using matrix-assisted laser desorption/ionisation spectrometry imaging. Results Asthmatic cells characterised by rate respiration with stimulated production β-oxidation. consumption . Proteome occurred via two canonical pathways. The carnitine palmitoyl transferase (CPT)2 low-density lipoprotein (LDL) receptor, which internalise acids through membranes, respectively, Blocking CPT2 or LDL receptor drastically specifically reduced Conclusion This demonstrates switch identifies as new key reduce