RT Journal Article
SR Electronic
T1 Effect of hypoxia on proliferation and VEGF-release of human bronchial smooth muscle cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P533
VO 42
IS Suppl 57
A1 Laura Keglowich
A1 Michael Roth
A1 Michael Tamm
A1 Pieter Borger
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P533.abstract
AB 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 ± 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 ± 18%; p = 0.033). The VEGF release from FCS-stimulated BSMC under hypoxia was significantly increased (3.58 ± 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.