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Metabolic and functional differences between male and female endothelial cells from umbilical cords (HUVEC) of twin pairs

Session Poster Session 1

Speaker Mario Lorenz

Event : ESC Congress 2019

  • Topic : basic science
  • Sub-topic : Basic Science - Vascular Biology and Physiology
  • Session type : Poster Session

Authors : M Lorenz (Berlin,DE), B Blaschke (Berlin,DE), A Benn (Berlin,DE), E Hammer (Greifswald,DE), E Witt (Greifswald,DE), J Kirwan (Berlin,DE), R Fritsche-Guenther (Berlin,DE), Y Gloaguen (Berlin,DE), F Kramer (Berlin,DE), K Kappert (Berlin,DE), P Brunner (Berlin,DE), H Dreger (Berlin,DE), K Stangl (Berlin,DE), P Knaus (Berlin,DE), V Stangl (Berlin,DE)

Authors:
M Lorenz1 , B Blaschke1 , A Benn2 , E Hammer3 , E Witt3 , J Kirwan4 , R Fritsche-Guenther4 , Y Gloaguen4 , F Kramer5 , K Kappert5 , P Brunner2 , H Dreger1 , K Stangl1 , P Knaus2 , V Stangl1 , 1Charite - University Medicine Berlin, Campus Mitte, Department of Cardiology and Angiology - Berlin - Germany , 2Free University, Institute for Chemistry and Biochemistry - Berlin - Germany , 3University Medicine of Greifswald, Interfaculty Institute for Genetics and Functional Genomics - Greifswald - Germany , 4Max Delbruck Center for Molecular Medicine, Berlin Institute of Health Metabolomics Platform - Berlin - Germany , 5Charite - University Medicine Berlin, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry - Berlin - Germany ,

Citation:

Background: Personalised Medicine is one of the hallmarks of future medicine. Sex and gender differences exist in the incidence, clinical manifestation and outcome of cardiovascular diseases. Gonadal hormones are thought to account for most of these sex differences. However, besides hormones, sexual dimorphisms at the cellular level may also contribute to physiological and pathophysiological cardiovascular differences between women and men.

Purpose: To analyse intrinsic sex differences at the cellular level, we aimed to elucidate sex-specific differences in endothelial cell migration and energy metabolism under pro-migratory conditions in male and female HUVECs. To reduce biological variability, we used HUVECS obtained from umbilical cords from twin pairs of the opposite sex. These cells are exposed in utero to the same maternal environment, and therefore represent a valuable tool to study intrinsic sex-specific differences at the cellular level.

Methods: Vascular endothelial growth factor (VEGF)-stimulated migration was determined with IBIDI migration chambers. Sex-specific levels of proteins were studied using proteome profiling. Cellular metabolism was measured by Seahorse and levels of intracellular metabolites were analysed using GC-MS based technology.

Results: Female cells showed significantly higher VEGF-induced cell migration than male HUVECs. Proteomic profiling revealed a sex-specific response to VEGF treatment. Mitochondrial respiration rate was higher in VEGF-stimulated male HUVECs compared to female cells. Whereas mean glycolytic rates did not significantly differ between sexes, the ratio of glycolysis/mitochondrial respiration after VEGF stimulation was higher in female than in male HUVECs. Female cells had higher intracellular ATP levels after serum starvation and treatment with VEGF. Under both conditions, female cells showed altered levels of metabolite pools compared to male HUVECs.

Conclusions: Higher intracellular ATP and metabolite levels in female cells after serum starvation and VEGF may contribute to the observed functional sexual dimorphisms, and may also point to an increased stress tolerance of female cells. The results of our study provide a strong argument to discriminate between male and female cells in in vitro experiments.

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