Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells.
Despite the well-established sex-specific differences in the incidence of bronchopulmonary dysplasia (BPD), the molecular mechanism(s) behind these are not completely understood. Pulmonary angiogenesis is critical for alveolarization and arrest in vascular development adversely affects lung development. Human neonatal umbilical vein endothelial cells (HUVECs) provide a robust in vitro model for the study of endothelial cell physiology and function. Male and Female HUVECs were exposed to room air (21% O2, 5% CO2) or hyperoxia (95% O2, 5% CO2) for up to 72 h. Cell viability, proliferation, H2O2production and angiogenesis were analyzed. Sex-specific differences in the expression of VEGFR2 and modulation of NF-kappa B pathway were measured. Male HUVECs have decreased survival, greater oxidative stress and impairment in angiogenesis compared to similarly exposed female cells. There is differential expression of VEGFR2 between male and female HUVECs and greater activation of the NF-kappa B pathway in female HUVECs under hyperoxic conditions. The results indicate that sex differences exist between male and female HUVECs in vitro after hyperoxia exposure. Since endothelial dysfunction has a major role in the pathogenesis of BPD, these differences could explain in part the mechanisms behind sex-specific differences in the incidence of this disease.
Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA. Electronic address: zhang@bcm.edu.
Yuhao
Y
Zhang
Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA. Electronic address: lingappa@bcm.edu.
Krithika
K
Lingappan
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018496:Hyperoxia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000633:toxicity*; D012737:Sex Factors; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism
D016328:NF-kappa B; D006861:Hydrogen Peroxide; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen
Angiogenesis; Bronchopulmonary dysplasia; HUVEC; Hyperoxia; Sex