Sex-specific eNOS activity and function in human endothelial cells

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...

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Bibliographic Details
Published in:Scientific reports 2017-08, Vol.7 (1), p.9612-13, Article 9612
Main Authors: Cattaneo, Maria Grazia, Vanetti, Claudia, Decimo, Ilaria, Di Chio, Marzia, Martano, Giuseppe, Garrone, Giulia, Bifari, Francesco, Vicentini, Lucia Maria
Format: Article
Language:English
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Angiogenesis
Cardiovascular diseases
Cell proliferation
Endothelial cells
Enzymatic activity
Humanities and Social Sciences
mRNA
multidisciplinary
Nitric oxide
Nitric-oxide synthase
Science
Science (multidisciplinary)
Sexual dimorphism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-10139-x