Mario Lorenz1, Benjamin Blaschke1, Andreas Benn2, Elke Hammer3, Eric Witt3, Jennifer Kirwan4, Raphaela Fritsche-Guenther4, Yoann Gloaguen5, Cornelia Bartsch6, Angelika Vietzke6, Frederike Kramer7, Kai Kappert8, Patrizia Brunner2, Hoang Giang Nguyen7, Henryk Dreger1, Karl Stangl6, Petra Knaus2, Verena Stangl9. 1. Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany. 2. Institut für Chemie und Biochemie, Freie Universität Berlin, Germany; Berlin School of Integrative Oncology (DFG Graduate School 1093), Germany. 3. Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Abteilung für Funktionelle Genomforschung, Universitätsmedizin Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Germany. 4. Berlin Institute of Health Metabolomics Platform, Berlin Institute of Health (BIH), Berlin, Germany; Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany. 5. Berlin Institute of Health Metabolomics Platform, Berlin Institute of Health (BIH), Berlin, Germany; Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany; Core Unit Bioinformatics, Berlin Institute of Health (BIH), 10178, Berlin, Germany. 6. Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Berlin, Germany. 7. Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Center for Cardiovascular Research (CCR), Berlin, Germany. 8. DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany; Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Center for Cardiovascular Research (CCR), Berlin, Germany. 9. Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany. Electronic address: verena.stangl@charite.de.
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.
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.
Authors: Brian A Aguado; Cierra J Walker; Joseph C Grim; Megan E Schroeder; Dilara Batan; Brandon J Vogt; Andrea Gonzalez Rodriguez; Jessica A Schwisow; Karen S Moulton; Robert M Weiss; Donald D Heistad; Leslie A Leinwand; Kristi S Anseth Journal: Circulation Date: 2022-01-10 Impact factor: 29.690
Authors: Raphaela Fritsche-Guenther; Yoann Gloaguen; Anna Bauer; Tobias Opialla; Stefan Kempa; Christina A Fleming; Henry Paul Redmond; Jennifer A Kirwan Journal: Metabolites Date: 2021-12-18