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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 2697364, 15 pages
Research Article

VLDL Induced Modulation of Nitric Oxide Signalling and Cell Redox Homeostasis in HUVEC

1Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy
2Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Ciencias Biológicas, Cátedra de Biología Celular y Molecular, Buenos Aires, Argentina
3Blood Transfusion Service and Hematology, Umberto I Hospital, Rome, Italy
4Department of Analytical Chemistry, Applied Chemometrics and Molecular Modelling, Vrije Universiteit Brussel, Brussels, Belgium

Correspondence should be addressed to Graciela Cristina Calabrese; ra.abu.byff@ebalacg and Marzia Arese; ti.1amorinu@esera.aizram

Received 21 April 2017; Revised 31 July 2017; Accepted 15 August 2017; Published 20 September 2017

Academic Editor: Vicenta L. Cortes

Copyright © 2017 Maria Chiara Magnifico et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


High levels of circulating lipoprotein constitute a risk factor for cardiovascular diseases, and in this context, the specific role of the very-low-density lipoproteins (VLDL) is poorly understood. The response of human umbilical vein endothelial cells (HUVEC) to VLDL exposure was studied, especially focusing on the pathways involved in alteration of redox homeostasis and nitric oxide (NO) bioavailability. The results obtained by the analysis of the expression level of genes implicated in the NO metabolism and oxidative stress response indicated a strong activation of inducible NO synthase (iNOS) upon 24 h exposure to VLDL, particularly if these have been preventively oxidised. Simultaneously, both mRNA and protein expression of endothelial NO synthase (eNOS) were decreased and its phosphorylation pattern, at the key residues Tyr495 and Ser1177, strongly suggested the occurrence of the eNOS uncoupling. The results are consistent with the observed increased production of nitrites and nitrates (NOx), reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), and, at mitochondrial level, a deficit in mitochondrial O2 consumption. Altogether, these data suggest that the VLDL, particularly if oxidised, when allowed to persist in contact with endothelial cells, strongly alter NO bioavailability, affecting redox homeostasis and mitochondrial function.