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

Oxidative Medicine and Cellular Longevity
Maria Chiara MagnificoMarzia Arese

Abstract

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...Continue Reading

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Citations

May 29, 2018·Oxidative Medicine and Cellular Longevity·Maria Chiara MagnificoMarzia Arese
Feb 23, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Cesar EcheverriaFelipe Simon

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Methods Mentioned

BETA
electrophoresis
Assay
Fluorescence
ELISA

Software Mentioned

DatLab
[UNK] MP Image Analysis

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