Sex-specific eNOS activity and function in human endothelial cells

Maria Grazia Cattaneo, Claudia Vanetti, Ilaria Decimo, Marzia Di Chio, Giuseppe Martano, Giulia Garrone, Francesco Bifari, Lucia Maria Vicentini

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Abstract

Clinical and epidemiological data show that biological sex is one of the major determinants for the development and progression of cardiovascular disease (CVD). Impaired endothelial function, characterized by an imbalance in endothelial Nitric Oxide Synthase (eNOS) activity, precedes and accelerates the development of CVD. However, whether there is any sexual dimorphism in eNOS activity and function in endothelial cells (ECs) is still unknown. Here, by independently studying human male and female ECs, we found that female ECs expressed higher eNOS mRNA and protein levels both in vitro and ex vivo. The increased eNOS expression was associated to higher enzymatic activity and nitric oxide production. Pharmacological and genetic inhibition of eNOS affected migratory properties only in female ECs. In vitro angiogenesis experiments confirmed that sprouting mostly relied on eNOS-dependent migration in female ECs. At variance, capillary outgrowth from male ECs was independent of eNOS activity but required cell proliferation. In this study, we found sex-specific differences in the EC expression, activity, and function of eNOS. This intrinsic sexual dimorphism of ECs should be further evaluated to achieve more effective and precise strategies for the prevention and therapy of diseases associated to an impaired endothelial function such as CVD and pathological angiogenesis.

Original languageEnglish
Article number9612
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Nitric Oxide Synthase Type III
Endothelial Cells
Sex Characteristics
Cardiovascular Diseases
Pathologic Neovascularization
Nitric Oxide
Cell Proliferation
Pharmacology
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Cattaneo, M. G., Vanetti, C., Decimo, I., Di Chio, M., Martano, G., Garrone, G., ... Vicentini, L. M. (2017). Sex-specific eNOS activity and function in human endothelial cells. Scientific Reports, 7(1), [9612]. https://doi.org/10.1038/s41598-017-10139-x

Sex-specific eNOS activity and function in human endothelial cells. / Cattaneo, Maria Grazia; Vanetti, Claudia; Decimo, Ilaria; Di Chio, Marzia; Martano, Giuseppe; Garrone, Giulia; Bifari, Francesco; Vicentini, Lucia Maria.

In: Scientific Reports, Vol. 7, No. 1, 9612, 01.12.2017.

Research output: Contribution to journalArticle

Cattaneo, MG, Vanetti, C, Decimo, I, Di Chio, M, Martano, G, Garrone, G, Bifari, F & Vicentini, LM 2017, 'Sex-specific eNOS activity and function in human endothelial cells', Scientific Reports, vol. 7, no. 1, 9612. https://doi.org/10.1038/s41598-017-10139-x
Cattaneo MG, Vanetti C, Decimo I, Di Chio M, Martano G, Garrone G et al. Sex-specific eNOS activity and function in human endothelial cells. Scientific Reports. 2017 Dec 1;7(1). 9612. https://doi.org/10.1038/s41598-017-10139-x
Cattaneo, Maria Grazia ; Vanetti, Claudia ; Decimo, Ilaria ; Di Chio, Marzia ; Martano, Giuseppe ; Garrone, Giulia ; Bifari, Francesco ; Vicentini, Lucia Maria. / Sex-specific eNOS activity and function in human endothelial cells. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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