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Intrapulmonary airway smooth muscle is hyperreactive with a distinct proteome in asthma
Gijs Ijpma1,2, Linda Kachmar1,2, Alice Panariti1,2
1Dept of Medicine, McGill University, Montreal, QC, Canada.
The European Respiratory Journal
|April 18, 2020
Summary
Airway smooth muscle (ASM) in asthma is hyperreactive, showing increased contractile stress and stiffness in intrapulmonary airways. This hyperreactivity, linked to specific protein changes, offers new therapeutic targets for asthma treatment.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Biochemistry
Background:
- Airway smooth muscle (ASM) contraction causes airway constriction during asthma exacerbations.
- It remains debated whether airway hyperresponsiveness (AHR) in asthma stems from increased ASM mass or enhanced force generation.
- Understanding ASM contractility is crucial for developing targeted asthma therapies.
Purpose of the Study:
- To investigate whether ASM is hypercontractile in human asthma.
- To identify proteomic changes in ASM and whole airways that may contribute to altered ASM properties.
- To determine if increased ASM mass or enhanced force generation underlies AHR in asthma.
Main Methods:
- Mechanical measurements of isolated ASM and whole airways from human lungs.
- Proteomic analysis of ASM and whole airway tissues using mass spectrometry.
- Principal Component Analysis (PCA) to identify proteomic differences between asthmatic and non-asthmatic subjects.
Main Results:
- Isolated asthmatic ASM from intrapulmonary bronchi exhibited increased contractile stress and stiffness.
- No alterations were observed in other contractile parameters or myosin activity regulation.
- Proteomic analysis revealed distinct clustering of asthmatic subjects and upregulation of structural proteins in whole airways.
Conclusions:
- ASM is hyperreactive in the intrapulmonary airways of asthmatic individuals.
- Upregulated proteins in asthmatic ASM may contribute to hyperreactivity.
- Enhanced force transmission, potentially due to structural protein enrichment, is suggested in asthmatic airways, opening new therapeutic avenues.
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