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Sex-specific metabolic and functional differences in human umbilical vein endothelial cells from twin pairs
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 seru…
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“For example, as human umbilical vein endothelial cells (HUVECs) are obtained from the umbilical cord, they are not only influenced by maternal hormones but also affected by embryonic gonads.”
From Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges (2024) · cites this paper as [10]
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Research works printed but not linked: 42
- Shen, 2017, Race and sex differences of long-term blood pressure profiles from childhood and adult hypertension: the Bogalusa Heart Study, Hypertension, 70, 66, 10.1161/HYPERTENSIONAHA.117.09537 · DOI
- Humphries, 2017, Sex differences in cardiovascular disease - impact on care and outcomes, Front. Neuroendocrinol., 46, 46, 10.1016/j.yfrne.2017.04.001 · DOI
- Regitz-Zagrosek, 2016, Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes, Eur. Heart J., 37, 24, 10.1093/eurheartj/ehv598 · DOI
- Jochmann, 2005, Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases, Eur. Heart J., 26, 1585, 10.1093/eurheartj/ehi397 · DOI
- Ventura-Clapier, 2017, Sex in basic research: concepts in the cardiovascular field, Cardiovasc. Res., 113, 711, 10.1093/cvr/cvx066 · DOI
- Straface, 2012, Sex differences at cellular level: “cells have a sex”, Handb. Exp. Pharmacol., 214, 49, 10.1007/978-3-642-30726-3_3 · DOI
- Mudrovcic, 2017, Endothelial maintenance in health and disease: importance of sex differences, Pharmacol. Res., 119, 48, 10.1016/j.phrs.2017.01.011 · DOI
- De Souza Santos, 2018, Sex and media: considerations for cell culture studies, ALTEX, 35, 435, 10.14573/altex.1806151 · DOI
- Ritz, 2014, First steps for integrating sex and gender considerations into basic experimental biomedical research, FASEB J., 28, 4, 10.1096/fj.13-233395 · DOI
- Kränkel, 2014, Novel insights into vascular repair mechanisms, Curr. Pharmaceut. Des., 20, 2430, 10.2174/13816128113199990478 · DOI
- Herbert, 2011, Molecular control of endothelial cell behavior during blood vessel morphogenesis, Nat. Rev. Mol. Cell Biol., 12, 551, 10.1038/nrm3176 · DOI
- Lorenz, 2015, Does cellular sex matter? Dimorphic transcriptional differences between female and male endothelial cells, Atherosclerosis, 240, 61, 10.1016/j.atherosclerosis.2015.02.018 · DOI · Paper page
- Zhang, 2017, Differential sex-specific effects of oxygen toxicity in human umbilical vein endothelial cells, Biochem. Biophys. Res. Commun., 486, 431, 10.1016/j.bbrc.2017.03.058 · DOI · Paper page
- Addis, 2014, Human umbilical endothelial cells (HUVECs) have a sex: characterisation of the phenotype of male and female cells, Biol. Sex Differ., 5, 18, 10.1186/s13293-014-0018-2 · DOI · Paper page
- Cattaneo, 2017, Sex-specific eNOS activity and function in human endothelial cells, Sci. Rep., 7, 9612, 10.1038/s41598-017-10139-x · DOI
- Bautch, 2012, VEGF-directed blood vessel patterning: from cells to organism, Cold Spring Harb. Perspect. Med., 2, 10.1101/cshperspect.a006452 · DOI
- Cruys, 2016, Glycolytic regulation of cell rearrangement in angiogenesis, Nat. Commun., 7, 12240, 10.1038/ncomms12240 · DOI
- Witt, 2019, Sex-specific differences in the intracellular proteome of human endothelial cells from dizygotic twins, J. Proteom., 201, 48, 10.1016/j.jprot.2019.03.016 · DOI
- Benn, 2017, Role of bone morphogenetic proteins in sprouting angiogenesis: differential BMP receptor-dependent signaling pathways balance stalk vs. tip cell competence, FASEB J., 31, 4720, 10.1096/fj.201700193RR · DOI
- Welshons, 1988, Estrogenic activity of phenol red, Mol. Cell. Endocrinol., 57, 169, 10.1016/0303-7207(88)90072-X · DOI
- Nakayama, 2013, Spatial regulation of VEGF receptor endocytosis in angiogenesis, Nat. Cell Biol., 15, 249, 10.1038/ncb2679 · DOI
- Cao, 2009, Positive and negative modulation of angiogenesis by VEGFR1 ligands, Sci. Signal., 2, 10.1126/scisignal.259re1 · DOI
- Michaelis, 2014, Mechanisms of endothelial cell migration, Cell. Mol. Life Sci., 71, 4131, 10.1007/s00018-014-1678-0 · DOI
- Hoetzer, 2007, Gender differences in circulating endothelial progenitor cell colony-forming capacity and migratory activity in middle-aged adults, Am. J. Cardiol., 99, 46, 10.1016/j.amjcard.2006.07.061 · DOI
- Huxley, 2018, Sex differences influencing micro- and macrovascular endothelial phenotype in vitro, J. Physiol., 596, 3929, 10.1113/JP276048 · DOI
- Salani, 2000, Endothelin-1 induces an angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo, Am. J. Pathol., 157, 1703, 10.1016/S0002-9440(10)64807-9 · DOI
- Heo, 2010, Expression profiling of ETS and MMP factors in VEGF-activated endothelial cells: role of MMP-10 in VEGF-induced angiogenesis, J. Cell. Physiol., 224, 734, 10.1002/jcp.22175 · DOI
- Potente, 2017, The link between angiogenesis and endothelial metabolism, Annu. Rev. Physiol., 79, 43, 10.1146/annurev-physiol-021115-105134 · DOI
- Vallerie, 2015, Metabolic flexibility and dysfunction in cardiovascular cells, Arterioscler. Thromb. Vasc. Biol., 35, e37, 10.1161/ATVBAHA.115.306226 · DOI
- de Bock, 2013, Role of PFKFB3-driven glycolysis in vessel sprouting, Cell, 154, 651, 10.1016/j.cell.2013.06.037 · DOI
- Wright, 2016, ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling, Science, 352, 1221, 10.1126/science.aad9335 · DOI
- Vanetti, 2017, Fatty acids rather than hormones restore in vitro angiogenesis in human male and female endothelial cells cultured in charcoal-stripped serum, PLoS One, 12, 10.1371/journal.pone.0189528 · DOI
- Ruoppolo, 2014, Serum metabolomic profiles suggest influence of sex and oral contraceptive use, Am. J. Transl. Res., 6, 614
- Mittelstrass, 2011, Discovery of sexual dimorphisms in metabolic and genetic biomarkers, PLoS Genet., 7, 10.1371/journal.pgen.1002215 · DOI
- Krumsiek, 2015, Gender-specific pathway differences in the human serum metabolome, Metabolomics, 11, 1815, 10.1007/s11306-015-0829-0 · DOI
- Piontek, 2017, Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes, Sci. Rep., 7, 2235, 10.1038/s41598-017-02367-y · DOI
- Rudnicki, 2018, Female mice have higher angiogenesis in perigonadal adipose tissue than males in response to high-fat diet, Front. Physiol., 9, 1452, 10.3389/fphys.2018.01452 · DOI
- Jeschke, 2005, Endogenous anabolic hormones and hypermetabolism: effect of trauma and gender differences, Ann. Surg., 241, 759, 10.1097/01.sla.0000161028.43338.cd · DOI
- Emmerson, 2012, The role of estrogen deficiency in skin ageing and wound healing, Biogerontology, 13, 3, 10.1007/s10522-011-9322-y · DOI · Paper page
- Akishita, 2012, Hormonal effects on blood vessels, Hypertens. Res., 35, 363, 10.1038/hr.2012.4 · DOI
- Gilliver, 2008, Sex dimorphism in wound healing: the roles of sex steroids and macrophage migration inhibitory factor, Endocrinology, 149, 5747, 10.1210/en.2008-0355 · DOI
- Rønø, 2013, Gender affects skin wound healing in plasminogen deficient mice, PLoS One, 8, 10.1371/journal.pone.0059942 · DOI
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Metadata
- Authors
- Lorenz, M., Blaschke, B., Benn, A., Hammer, E., Witt, E., Kirwan, J., Fritsche-Guenther, R., Gloaguen, Y., Bartsch, C., Vietzke, A., Kramer, F., Kappert, K., Brunner, P., Nguyen, H. G., Dreger, H., Stangl, K., Knaus, P., & Stangl, V.
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 291
- Pages
- 99-106
- ISSN
- 0021-9150
- Cited by
- 39
- References
- 0
- Language
- en
- Funders
- Deutsches Zentrum für Herz-Kreislaufforschung
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung (81X2100211)
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