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Sex-specific metabolic and functional differences in human umbilical vein endothelial cells from twin pairs

Item Type:Article
Title:Sex-specific metabolic and functional differences in human umbilical vein endothelial cells from twin pairs
Creators Name:Lorenz, M. and Blaschke, B. and Benn, A. and Hammer, E. and Witt, E. and Kirwan, J. and Fritsche-Guenther, R. and Gloaguen, Y. and Bartsch, C. and Vietzke, A. and Kramer, F. and Kappert, K. and Brunner, P. and Nguyen, H.G. and Dreger, H. and Stangl, K. and Knaus, P. and Stangl, V.
Abstract:BACKGROUND AND AIMS: Gonadal hormones are mainly thought to account for sex and gender differences in the incidence, clinical manifestation and therapy of many cardiovascular diseases. However, intrinsic sex differences at the cellular level are mostly overlooked. Here, we assessed sex-specific metabolic and functional differences between male and female human umbilical vein endothelial cells (HUVECs). METHODS: Cellular metabolism was investigated by bioenergetic studies (Seahorse Analyser) and a metabolomic approach. Protein levels were determined by Western blots and proteome analysis. Vascular endothelial growth factor (VEGF)-stimulated cellular migration was assessed by gap closure. HUVECs from dizygotic twin pairs were used for most experiments. RESULTS: No sex differences were observed in untreated cells. However, sexual dimorphisms appeared after stressing the cells by serum starvation and treatment with VEGF. Under both conditions, female cells had higher intracellular ATP and metabolite levels. A significant decline in ATP levels was observed in male cells after serum starvation. After VEGF, the ratio of glycolysis/mitochondrial respiration was higher in female cells and migration was more pronounced. CONCLUSIONS: These results point to an increased stress tolerance of female cells. We therefore propose that female cells have an energetic advantage over male cells under conditions of diminished nutrient supply. A more favourable energy balance of female HUVECs after serum starvation and VEGF could potentially explain their stronger migratory capacity.
Keywords:Sex-Specific, Metabolism, Proteome, Migration, Endothelial Cell
Source:Atherosclerosis
ISSN:0021-9150
Publisher:Elsevier (Ireland)
Volume:291
Page Range:99-106
Date:10 October 2019
Official Publication:https://doi.org/10.1016/j.atherosclerosis.2019.10.007
PubMed:View item in PubMed

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