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Extra virgin olive oil rich in polyphenols modulates VEGF-induced angiogenic responses by preventing NADPH oxidase activity and expression
Institution:1. National Research Council - Institute of Clinical Physiology, Lecce, Italy;2. Clinica Medica \"A. Murri\", University of Bari Medical School, Italy;3. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Italy;4. Department of Biological and Environmental Science and Technologies, University of Lecce, Italy;5. “G. Monasterio” Foundation for Clinical Research, Pisa, Italy;6. “G. d’Annunzio” University and Center of Excellence on Aging, Chieti, Italy;1. Neonatal Intensive Care Unit, Dr. Sami Ulus Maternity and Children Research and Training Hospital, Ankara, Turkey;2. Pediatric Ophthalmology Unit, Dr. Sami Ulus Maternity and Children Research and Training Hospital, Ankara, Turkey;1. Henan Joint International Research Laboratory of Stem Cell Medicine, College of Biomedical Engineering, Xinxiang Medical University, Xinxiang 453003, Henan, China;2. Children''s Heart Center, the Second Affiliated Hospital and Yuying Children''s Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Wenzhou 325000, China;3. Stem Cell and Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, Henan, China;4. School of psychology, Xinxiang Medical University, Xinxiang 453003, Henan, China;5. Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan, China;6. Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Psychiatric Hospital of Henan province, China), Xinxiang 453002, Henan, China;7. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, China
Abstract:Previous studies have shown the antiinflammatory, antioxidant and antiangiogenic properties by pure olive oil polyphenols; however, the effects of olive oil phenolic fraction on the inflammatory angiogenesis are unknown. In this study, we investigated the effects of the phenolic fraction (olive oil polyphenolic extract, OOPE) from extra virgin olive oil and related circulating metabolites on the VEGF-induced angiogenic responses and NADPH oxidase activity and expression in human cultured endothelial cells. We found that OOPE (1–10 μg/ml), at concentrations achievable nutritionally, significantly reduced, in a concentration-dependent manner, the VEGF-induced cell migration, invasiveness and tube-like structure formation through the inhibition of MMP-2 and MMP-9. OOPE significantly (P<0.05) reduced VEGF-induced intracellular reactive oxygen species by modulating NADPH oxidase activity, p47phox membrane translocation and the expression of Nox2 and Nox4. Moreover, the treatment of endothelial cells with serum obtained 4 h after acute intake of extra virgin olive oil, with high polyphenol content, decreased VEGF-induced NADPH oxidase activity and Nox4 expression, as well as, MMP-9 expression, as compared with fasting control serum. Overall, native polyphenols and serum metabolites of extra virgin olive oil rich in polyphenols are able to lower the VEGF-induced angiogenic responses by preventing endothelial NADPH oxidase activity and decreasing the expression of selective NADPH oxidase subunits. Our results provide an alternative mechanism by which the consumption of olive oil rich in polyphenols may account for a reduction of oxidative stress inflammatory-related sequelae associated with chronic degenerative diseases.
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