Obesity increases airway smooth muscle responses to contractile agonists

Sarah Orfanos, Joseph Jude, Brian T. Deeney, Gaoyuan Cao, Deepa Rastogi, Mark van Zee, Ivan Pushkarsky, Hector E. Munoz, Robert Damoiseaux, Dino Di Carlo, Reynold A. Panettieri

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)L673-L681
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume315
Issue number5
DOIs
StatePublished - Nov 2018

Keywords

  • Asthma
  • Body mass index
  • Obesity
  • Remodeling
  • Wheezing

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Orfanos, S., Jude, J., Deeney, B. T., Cao, G., Rastogi, D., van Zee, M., Pushkarsky, I., Munoz, H. E., Damoiseaux, R., Di Carlo, D., & Panettieri, R. A. (2018). Obesity increases airway smooth muscle responses to contractile agonists. American Journal of Physiology - Lung Cellular and Molecular Physiology, 315(5), L673-L681. https://doi.org/10.1152/ajplung.00459.2017