Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 39

The DOI matches its Crossref record.

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

Lorenz, Mario, Blaschke, Benjamin, Benn, Andreas, Hammer, Elke, Witt, Eric, Kirwan, Jennifer, Fritsche-Guenther, Raphaela, Gloaguen, Yoann, Bartsch, Cornelia, Vietzke, Angelika, Kramer, Frederike, Kappert, Kai, Brunner, Patrizia, Nguyen, Hoang Giang, Dreger, Henryk, Stangl, Karl, Knaus, Petra, Stangl, Verena·2019·Atherosclerosis
DOI 10.1016/j.atherosclerosis.2019.10.007
Open this paper in CoChat — free account

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…

Overview

Integrity signals

Registry

Crossref · 10.1016/j.atherosclerosis.2019.10.007

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 42

  1. 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
  2. Humphries, 2017, Sex differences in cardiovascular disease - impact on care and outcomes, Front. Neuroendocrinol., 46, 46, 10.1016/j.yfrne.2017.04.001 · DOI
  3. Regitz-Zagrosek, 2016, Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes, Eur. Heart J., 37, 24, 10.1093/eurheartj/ehv598 · DOI
  4. Jochmann, 2005, Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases, Eur. Heart J., 26, 1585, 10.1093/eurheartj/ehi397 · DOI
  5. Ventura-Clapier, 2017, Sex in basic research: concepts in the cardiovascular field, Cardiovasc. Res., 113, 711, 10.1093/cvr/cvx066 · DOI
  6. 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
  7. Mudrovcic, 2017, Endothelial maintenance in health and disease: importance of sex differences, Pharmacol. Res., 119, 48, 10.1016/j.phrs.2017.01.011 · DOI
  8. De Souza Santos, 2018, Sex and media: considerations for cell culture studies, ALTEX, 35, 435, 10.14573/altex.1806151 · DOI
  9. 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
  10. Kränkel, 2014, Novel insights into vascular repair mechanisms, Curr. Pharmaceut. Des., 20, 2430, 10.2174/13816128113199990478 · DOI
  11. Herbert, 2011, Molecular control of endothelial cell behavior during blood vessel morphogenesis, Nat. Rev. Mol. Cell Biol., 12, 551, 10.1038/nrm3176 · DOI
  12. 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
  13. 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
  14. 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
  15. Cattaneo, 2017, Sex-specific eNOS activity and function in human endothelial cells, Sci. Rep., 7, 9612, 10.1038/s41598-017-10139-x · DOI
  16. Bautch, 2012, VEGF-directed blood vessel patterning: from cells to organism, Cold Spring Harb. Perspect. Med., 2, 10.1101/cshperspect.a006452 · DOI
  17. Cruys, 2016, Glycolytic regulation of cell rearrangement in angiogenesis, Nat. Commun., 7, 12240, 10.1038/ncomms12240 · DOI
  18. 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
  19. 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
  20. Welshons, 1988, Estrogenic activity of phenol red, Mol. Cell. Endocrinol., 57, 169, 10.1016/0303-7207(88)90072-X · DOI
  21. Nakayama, 2013, Spatial regulation of VEGF receptor endocytosis in angiogenesis, Nat. Cell Biol., 15, 249, 10.1038/ncb2679 · DOI
  22. Cao, 2009, Positive and negative modulation of angiogenesis by VEGFR1 ligands, Sci. Signal., 2, 10.1126/scisignal.259re1 · DOI
  23. Michaelis, 2014, Mechanisms of endothelial cell migration, Cell. Mol. Life Sci., 71, 4131, 10.1007/s00018-014-1678-0 · DOI
  24. 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
  25. Huxley, 2018, Sex differences influencing micro- and macrovascular endothelial phenotype in vitro, J. Physiol., 596, 3929, 10.1113/JP276048 · DOI
  26. 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
  27. 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
  28. Potente, 2017, The link between angiogenesis and endothelial metabolism, Annu. Rev. Physiol., 79, 43, 10.1146/annurev-physiol-021115-105134 · DOI
  29. Vallerie, 2015, Metabolic flexibility and dysfunction in cardiovascular cells, Arterioscler. Thromb. Vasc. Biol., 35, e37, 10.1161/ATVBAHA.115.306226 · DOI
  30. de Bock, 2013, Role of PFKFB3-driven glycolysis in vessel sprouting, Cell, 154, 651, 10.1016/j.cell.2013.06.037 · DOI
  31. Wright, 2016, ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling, Science, 352, 1221, 10.1126/science.aad9335 · DOI
  32. 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
  33. Ruoppolo, 2014, Serum metabolomic profiles suggest influence of sex and oral contraceptive use, Am. J. Transl. Res., 6, 614
  34. Mittelstrass, 2011, Discovery of sexual dimorphisms in metabolic and genetic biomarkers, PLoS Genet., 7, 10.1371/journal.pgen.1002215 · DOI
  35. Krumsiek, 2015, Gender-specific pathway differences in the human serum metabolome, Metabolomics, 11, 1815, 10.1007/s11306-015-0829-0 · DOI
  36. 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
  37. 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
  38. 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
  39. 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
  40. Akishita, 2012, Hormonal effects on blood vessels, Hypertens. Res., 35, 363, 10.1038/hr.2012.4 · DOI
  41. 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
  42. Rønø, 2013, Gender affects skin wound healing in plasminogen deficient mice, PLoS One, 8, 10.1371/journal.pone.0059942 · DOI

Cited by

See all 39

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.
ORCID
Venue
Atherosclerosis
Publisher
Elsevier BV
Published
2019-12
Volume
291
Pages
99-106
ISSN
0021-9150
DOI
10.1016/j.atherosclerosis.2019.10.007
Cited by
39
References
0
Language
en
Licence
Funders
  • Deutsches Zentrum für Herz-Kreislaufforschung
  • Deutsche Forschungsgemeinschaft
  • Bundesministerium für Bildung und Forschung (81X2100211)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Sex-specific metabolic and functional differences in human umbilical vein endothelial cells from twin pairs. https://app.cochat.ai/papers/10.1016/j.atherosclerosis.2019.10.007
The paper
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. (2019). Sex-specific metabolic and functional differences in human umbilical vein endothelial cells from twin pairs. Atherosclerosis. https://doi.org/10.1016/j.atherosclerosis.2019.10.007