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Obesity increases airway smooth muscle responses to contractile agonists.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2018 Nov 01; Vol. 315 (5), pp. L673-L681. Date of Electronic Publication: 2018 Aug 30. - Publication Year :
- 2018
-
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.
- Subjects :
- Adult
Asthma etiology
Asthma metabolism
Calcium metabolism
Cardiotonic Agents pharmacology
Case-Control Studies
Cells, Cultured
Female
Histamine Agonists pharmacology
Humans
Male
Muscle, Smooth drug effects
Myosin Light Chains metabolism
Prognosis
Respiratory System drug effects
Asthma physiopathology
Carbachol pharmacology
Histamine pharmacology
Muscle Contraction drug effects
Muscle, Smooth pathology
Obesity complications
Respiratory System pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1504
- Volume :
- 315
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30160518
- Full Text :
- https://doi.org/10.1152/ajplung.00459.2017