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Effects of sex hormones on inflammatory response in male and female vascular endothelial cells

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Abstract

Purpose

Gender-related differences in sex hormones might have a key role in the development of atherosclerosis though direct vascular effects of sex hormones are not yet well understood. Thus, the main purpose of this study was to compare the effects of sex hormones on inflammatory response in Human Umbilical Vein Endothelial Cells (HUVECs) obtained from both male and female donors.

Methods

We analyzed the expression of receptors and enzymes relevant to the action of androgens (AR, 5α-reductase 1 and 5α-reductase 2) and estrogens (ERα, ERβ, and aromatase) in male and female HUVECs. Furthermore, we analyzed the effect of testosterone (T), 17β-estradiol (E2), dihydrotestosterone (DHT), and several androgenic-anabolic steroids (AAS) on VCAM-1, ICAM-1, and E-selectin gene expression and on adhesion of U937 cells to TNF-α-stimulated male and female HUVECs.

Results

Our results reveal that in HUVECs, regardless of gender, the components involved in the androgen action pathway are predominant as compared to those of estrogen action pathway. In both HUVEC genders, the inflammatory effect of TNF-α was amplified by co-administration of T or DHT and several AAS frequently used in doping, while E2 had no effect.

Conclusions

This is the first study analyzing, under identical culture conditions, the key components of sex hormone response in male and female HUVECs and the possible role of sex hormones in regulating the endothelial inflammatory response. The data obtained in our experimental system showed a pro-inflammatory effect of androgens, while conclusively excluding any protective effect for all the tested hormones.

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Acknowledgments

This study was supported by “Commissione per la vigilanza ed il controllo sul doping”, Italian Ministry of Health. We would like to thank GlaxoSmithKline which provided valuable reagents and Dr. Laura Guerra for linguistic help.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino Carlo Bo, Via I. Maggetti 26, 61029, Urbino, PU, Italy

    Giosuè Annibalini, Deborah Agostini, Cinzia Calcabrini, Chiara Martinelli, Evelin Colombo, Michele Guescini, Pasquale Tibollo, Vilberto Stocchi & Piero Sestili

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  1. Giosuè Annibalini
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  2. Deborah Agostini
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  3. Cinzia Calcabrini
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  4. Chiara Martinelli
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  5. Evelin Colombo
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  6. Michele Guescini
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  7. Pasquale Tibollo
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  8. Vilberto Stocchi
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  9. Piero Sestili
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Correspondence to Giosuè Annibalini.

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Annibalini, G., Agostini, D., Calcabrini, C. et al. Effects of sex hormones on inflammatory response in male and female vascular endothelial cells. J Endocrinol Invest 37, 861–869 (2014). https://doi.org/10.1007/s40618-014-0118-1

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  • DOI: https://doi.org/10.1007/s40618-014-0118-1

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