@article {KeglowichP533, author = {Laura Keglowich and Michael Roth and Michael Tamm and Pieter Borger}, title = {Effect of hypoxia on proliferation and VEGF-release of human bronchial smooth muscle cells}, volume = {42}, number = {Suppl 57}, elocation-id = {P533}, year = {2013}, publisher = {European Respiratory Society}, abstract = {Background: Airway wall remodeling, an important asthma pathology, includes basement membrane thickening. This may lead to hypoxia in the sub-epithelial cells layer. Increased levels of hypoxia-inducible factor alpha in endobronchial biopsies and BALF of asthmatics support this hypothesis.Objective: In our study we investigate the effect of hypoxia on proliferation of human bronchial smooth muscle cells (BSMC) and on the release of VEGF.Methods: BSMC have been stimulated with 5\% FCS under normoxic (21\% O2) or hypoxic (1\% O2) conditions. Proliferation was determined by cell counts. The release of VEGF from BSMC was analyzed by ELISA. Proliferating Cell Nuclear Antigen (PCNA) was detected by immunoblots.Results: Proliferation of FCS-stimulated BSMC was significantly increased. Hypoxia significantly reduced the FCS-induced proliferation by 56.70 {\textpm} 5.53\%. Analysis of protein levels of PCNA reflects the observed proliferation-inhibition. After 24h PCNA protein-levels of BSMC under hypoxic conditions significantly decreased (43 {\textpm} 18\%; p = 0.033). The VEGF release from FCS-stimulated BSMC under hypoxia was significantly increased (3.58 {\textpm} 0.66; p = 0.001).Conclusion: Hypoxia led to reduced proliferation of FCS-stimulated BSMC. BSMC hyperplasia, one feature of airway wall remodeling in asthmatics, can therefore not be linked directly to the proliferative stimulus of hypoxia as suggested by others. Our data suggest that BSMC hyperplasia in asthma is indirectly induced by hypoxia through VEGF-dependent angiogenesis and increased nutrition supply.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/42/Suppl_57/P533}, eprint = {https://erj.ersjournals.com/content/42/Suppl_57/P533.full.pdf}, journal = {European Respiratory Journal} }