|Proteomic analysis reveals different responses to hypoxia in male and female human pulmonary microvascular endothelial cells
|D. Kostyunina, E. Dillon, K. Rochfort, P. Cummins, P. McLoughlin
|Conway Institute, School of Medicine, University College Dublin
|Click to view poster
|General Respiratory and Sleep
|Pulmonary arterial hypertension (PAH) is a severe pulmonary disease which is more common in women. Sex hormone independent mechanisms were recently shown to contribute to the higher incidence in females but the specific mechanisms are unknown. Pulmonary endothelial cell abnormalities are central in the development of PAH and hypoxia is one of the stimuli that leads to these abnormalities. The aim of this study was to test the hypothesis that female predominance in PAH is due to different endothelial cell responses to hypoxia compared to males, which are independent of sex hormones.
Human pulmonary microvascular endothelial cells (HPMEC) from 3 male and 3 female age matched donors were placed either in normoxia or hypoxia (1%O2, 24/48 hours).
Proteomic data analysis revealed pathways that were enriched in females compared to males in hypoxia: “hypoxia”, “KRAS signalingDn”, “glycolysis”, “MYC targetsV2”, and “spermatogenesis”. Proteins that showed sex-dependent responses included thymosin-β 4 and glucose-6-phosphate-1-dehydrogenase, which X-chromosome linked, and previously implicated in PAH.
Proteomic analysis revealed that 1) hypoxic responses of female and male HPMEC are different 2) X chromosome linked proteins may play a role in the sex-dependent differences of HPMEC responses to hypoxia. These factors may contribute to the female predominance in PAH.