Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulm...

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Bibliographic Details
Published in:PloS one 2015-07, Vol.10 (7), p.e0129489-e0129489
Main Authors: Hartman, William, Helan, Martin, Smelter, Dan, Sathish, Venkatachalem, Thompson, Michael, Pabelick, Christina M, Johnson, Bruce, Prakash, Y S
Format: Article
Language:English
Subjects:
Anesthesiology
Apoptosis
Arteries
Biomedical engineering
Brain
Brain research
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - metabolism
Calcium (intracellular)
Calcium - metabolism
Cell growth
Cell Hypoxia - drug effects
Cell Proliferation - drug effects
Cell Survival - drug effects
Endothelium
Engineering
Gene Expression Regulation - drug effects
Growth factors
Humans
Hypertension
Hypoxia
Kinases
Lung diseases
Membrane Glycoproteins - metabolism
Muscles
Myocytes, Smooth Muscle - cytology
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - metabolism
Neurotrophic factors
Neutralization
Pathogenesis
Physiology
Protein-Tyrosine Kinases - metabolism
Proteins
Pulmonary arteries
Pulmonary artery
Pulmonary Artery - cytology
Pulmonary hypertension
Receptor, trkB
Rodents
Serotonin
Signaling
Smooth muscle
Structure-function relationships
Thoracic surgery
TrkB receptors
Vascular diseases
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Summary:Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in human pulmonary artery smooth muscle cells (PASMCs). 48h of 1% hypoxia enhanced BDNF and TrkB expression, as well as release of BDNF. In arteries of patients with pulmonary hypertension, BDNF expression and release was higher at baseline. In isolated PASMCs, hypoxia-induced BDNF increased intracellular Ca2+ responses to serotonin: an effect altered by HIF1α inhibition or by neutralization of extracellular BDNF via chimeric TrkB-Fc. Enhanced BDNF/TrkB signaling increased PASMC survival and proliferation, and decreased apoptosis following hypoxia. Enhanced expression and signaling of the BDNF-TrkB system in PASMCs is a potential mechanism by which hypoxia can promote changes in pulmonary artery structure and function. Accordingly, the BDNF-TrkB system could be a key player in the pathogenesis of hypoxia-induced pulmonary vascular diseases, and thus a potential target for therapy.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0129489