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Hydroxytyrosol Ameliorates Endothelial Function under Inflammatory Conditions by Preventing Mitochondrial Dysfunction
- Source :
- Oxidative Medicine and Cellular Longevity, Oxidative Medicine and Cellular Longevity, Vol 2018 (2018)
- Publication Year :
- 2017
-
Abstract
- Mitochondria are fundamental organelles producing energy and reactive oxygen species (ROS); their impaired functions play a key role in endothelial dysfunction. Hydroxytyrosol (HT), a well-known olive oil antioxidant, exerts health benefits against vascular diseases by improving endothelial function. However, the HT role in mitochondrial oxidative stress in endothelial dysfunction is not clear yet. To investigate the HT effects on mitochondrial ROS production in the inflamed endothelium, we used an in vitro model of endothelial dysfunction represented by cultured endothelial cells, challenged with phorbol myristate acetate (PMA), an inflammatory, prooxidant, and proangiogenic agent. We found that the pretreatment of endothelial cells with HT (1–30 μmol/L) suppressed inflammatory angiogenesis, a crucial aspect of endothelial dysfunction. The HT inhibitory effect is related to reduced mitochondrial superoxide production and lipid peroxidation and to increased superoxide dismutase activity. HT, in a concentration-dependent manner, improved endothelial mitochondrial function by reverting the PMA-induced reduction of mitochondrial membrane potential, ATP synthesis, and ATP5β expression. In PMA-challenged endothelial cells, HT also promoted mitochondrial biogenesis through increased mitochondrial DNA content and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A. These results highlight that HT blunts endothelial dysfunction and pathological angiogenesis by ameliorating mitochondrial function, thus suggesting HT as a potential mitochondria-targeting antioxidant in the inflamed endothelium.
- Subjects :
- 0301 basic medicine
Mitochondrial ROS
Aging
Endothelium
Article Subject
Angiogenesis
Neovascularization, Physiologic
Vascular Cell Adhesion Molecule-1
030204 cardiovascular system & hematology
Mitochondrion
medicine.disease_cause
Biochemistry
DNA, Mitochondrial
Hydroxythyrosol
Cell Line
03 medical and health sciences
0302 clinical medicine
Cell Movement
Superoxides
Malondialdehyde
medicine
Human Umbilical Vein Endothelial Cells
Humans
Endothelial dysfunction
lcsh:QH573-671
chemistry.chemical_classification
Membrane Potential, Mitochondrial
Reactive oxygen species
Chemistry
lcsh:Cytology
Superoxide Dismutase
Endothelial Cells
Cell Biology
General Medicine
Phenylethyl Alcohol
medicine.disease
Cell biology
Mitochondria
Angiogenesi
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Mitochondrial biogenesis
Tetradecanoylphorbol Acetate
Reactive Oxygen Species
Oxidative stress
Mitochondria disfunction
Research Article
Subjects
Details
- ISSN :
- 19420994
- Volume :
- 2018
- Database :
- OpenAIRE
- Journal :
- Oxidative medicine and cellular longevity
- Accession number :
- edsair.doi.dedup.....f5a22fc7c4962872862bca026391f36c