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Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1;315(5):L673-L681. doi: 10.1152/ajplung.00459.2017. Epub 2018 Aug 30.

Obesity increases airway smooth muscle responses to contractile agonists.

Author information

1
Rutgers Institute for Translational Medicine and Science, Child Health Institute of New Jersey, Rutgers, The State University of New Jersey , New Brunswick, New Jersey.
2
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
3
Department of Bioengineering, University of California , Los Angeles, California.
4
California NanoSystems Institute, University of California , Los Angeles, California.
5
Department of Mechanical Engineering, University of California , Los Angeles, California.

Abstract

The asthma-obesity syndrome represents a major public health concern that disproportionately contributes to asthma severity and induces insensitivity to therapy. To date, no study has shown an intrinsic difference between human airway smooth muscle (HASM) cells derived from nonobese subjects and those derived from obese subjects. The objective of this study was to address whether there is a greater response to agonist-induced calcium mobilization, phosphorylation of myosin light chain (MLC), and greater shortening in HASM cells derived from obese subjects. HASM cells derived from nonobese and obese subjects were age and sex matched. Phosphorylation of MLC was measured after having been stimulated by carbachol. Carbachol- or histamine-induced mobilization of calcium and cell shortening were assessed in HASM cells derived from nonobese and obese donors. Agonist-induced MLC phosphorylation, mobilization of calcium, and cell shortening were greater in obese compared with non-obese-derived HASM cells. The MLC response was comparable in HASM cells derived from obese nonasthma and nonobese fatal asthma subjects. HASM cells derived from obese female subjects were more responsive to carbachol than HASM cells derived from obese male subjects. Insulin pretreatment had little effect on these responses. Our results show an increase in agonist-induced calcium mobilization associated with an increase in MLC phosphorylation and an increase in ASM cell shortening in favor of agonist-induced hyperresponsiveness in HASM cells derived from obese subjects. Our studies suggest that obesity induces a retained phenotype of hyperresponsiveness in cultured human airway smooth muscle cells.

KEYWORDS:

asthma; body mass index; obesity; remodeling; wheezing

PMID:
30160518
PMCID:
PMC6295505
DOI:
10.1152/ajplung.00459.2017

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