title: Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle.
abstract: BACKGROUND
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, 55905, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Hartman
authors.affiliation: International Clinical Research Center, Department of Cardiovascular Diseases, St. Anne's University Hospital, Brno, Czech Republic; Department of Anesthesiology and Intensive Care, St. Anne's University Hospital, Masaryk University, Brno, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Helan
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, 55905, United States of America.
authors.forename: Dan
authors.initials: D
authors.lastname: Smelter
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, 55905, United States of America; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, 55905, United States of America.
authors.forename: Venkatachalem
authors.initials: V
authors.lastname: Sathish
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, 55905, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, 55905, United States of America; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, 55905, United States of America.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Pabelick
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, 55905, United States of America; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, 55905, United States of America.
authors.forename: Bruce
authors.initials: B
authors.lastname: Johnson
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, 55905, United States of America; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, 55905, United States of America.
authors.forename: Y S
authors.initials: YS
authors.lastname: Prakash
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology*; D020813:Receptor, trkB
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; C579455:BDNF protein, human; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human; D002118:Calcium