Oleic Acid Inhibits Endothelial Activation : A Direct Vascular Antiatherogenic Mechanism of a Nutritional Component in the Mediterranean Diet (original) (raw)
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Cardiovascular Diabetology, 2015
Background: Several translational studies have identified the differential role between saturated and unsaturated fatty acids at cardiovascular level. However, the molecular mechanisms that support the protective role of oleate in cardiovascular cells are poorly known. For these reasons, we studied the protective role of oleate in the insulin resistance and in the atherosclerotic process at cellular level such as in cardiomyocytes (CMs), vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). Methods: The effect of oleate in the cardiovascular insulin resistance, vascular dysfunction, inflammation, proliferation and apoptosis of VSMCs were analyzed by Western blot, qRT-PCR, BrdU incorporation and cell cycle analysis.
Trans Fatty Acids: Induction of a Pro-inflammatory Phenotype in Endothelial Cells
Lipids, 2012
Epidemiological data have shown an association of the intake of industrial produced trans fatty acids (TFA) and sudden cardiac death. The present study examines the impact of elaidic acid (t18:1n-9) and linoelaidic acid (t18:2n-6) on the human aortic endothelial cell functional response. Trans fatty acids predominately incorporated into the phospholipid component while only a minute fraction of the total fatty acids (FA) incorporated into triacylglycerol. Trans fatty acids incorporated into the plasma membranes at the expense of the saturated-FA, stearic, palmitic, and to a lesser extent, myristic acid. Both t18:1n-9 and t18:2n-6 induced a pro-inflammatory response by elevating surface expression of intercellular adhesion molecule-1 (ICAM-1). Neither oleic nor linoleic evoked a pro-inflammatory phenotype under the maximal 50 lM treatments. Both TFA and stearic acid increased phosphorylation of the ICAM-1 transcriptional regulator, nuclear factor-jb (NF-jb), while oleic and linoleic acids did not appear to alter the phosphorylation status. Elaidic acid minimally affected endothelial cell growth, whereas linoelaidic acid completely inhibited growth at 100 lM and imparted limited cytotoxicity up to 300 lM. Stearic acid induced cytotoxicity at concentrations above 75 lM, while oleic and linoleic acids evoked gradual dose-dependent growth inhibition with cytotoxicity occurring only at linoleic acid concentrations greater than 200 lM. In conclusion, t18:1n-9 and t18:2n-6 fatty acids effectively incorporated into the phospholipid component of endothelial cells and subsequently induce a pro-inflammatory phenotype.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2002
In a model of early atherogenesis based on cultured endothelial cells, we observed that the incorporation of oleic acid in cellular lipids decreases the stimulated expression of several endothelial adhesion molecules and soluble products typically expressed during endothelial activation and involved in monocyte recruitment.We investigated possible mechanisms for thiseffect assessing the stimulatedinduction of nuclear factor-kB.In parallel, we also measured glutathione (GSH) content and the activity of antioxidant enzymes after oleate treatment and cytokine stimulation. Oleate prevented the stimulated depletion of GSH without any change in the activity of antioxidant enzymes.These results suggest an antioxidant mechanism by which oleate may exert direct vascular atheroprotective effects. &
Palmitate and oleate have distinct effects on the inflammatory phenotype of human endothelial cells
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2007
Free fatty acids may create a state of continuous and progressive damaging to the vascular wall manifested by endothelial dysfunction. In this study we determine the mechanisms by which fatty acids palmitate (C16:0) and oleate (C18:1) affect intracellular long chain acyl-CoA (LCAC) content, energy metabolism, cell survival and proliferation and activation of NF-κB in cultured endothelial cells. A 48-h exposure of human umbilical vein endothelial cells (HUVEC) to 0.5 mM palmitate or 0.5 mM oleate increased total long chain acyl-CoA (LCAC) content 1.7 and 2 fold, respectively and decreased ATP total /ADP total ratio by 26 ± 5% (mean ± SEM) and 15 ± 2%, respectively, which was prevented by the acyl-CoA synthetase inhibitor triacsin C. Furthermore, palmitate inhibited cell proliferation by 34 ± 5%, while oleate stimulated it by 12 ± 2%. α-Tocopherol fully and triacsin C partially abolished the effect of palmitate on cell proliferation. Palmitate and oleate increased caspase-3 activity 3.2 and 1.4 fold, respectively. Palmitate-induced caspase-3 activation was prevented by triacsin C and slightly reduced by α-tocopherol and by the de novo ceramide synthesis inhibitor fumonisin B 1. Both fatty acids induced antioxidant-sensitive nuclear translocation of NF-κB after 72 h, but not after 48 h. In conclusion, we showed that fatty acids influence different aspects of HUVEC function resulting in amongst other activation of apoptotic and inflammatory pathways. Our results indicate that the effects depend on the fatty acid type and may be related to accumulation of LCAC.
An Overview of the Modulatory Effects of Oleic Acid in Health and Disease
Mini-Reviews in Medicinal Chemistry, 2013
Evidences in the last years have showed the effects of oleic acid (OA) in human health and disease. Olive oil, rich in oleic acid, is supposed to present modulatory effects in a wide physiological functions, while some studies also suggest a beneficial effect on cancer, autoimmune and inflammatory diseases, besides its ability to facilitate wound healing. Although the OA role in immune responses are still controversial, the administration of olive oil containing diets may improve the immune response associated to a more successful elimination of pathogens such as bacteria and fungi, by interfering in many components of this system such as macrophages, lymphocytes and neutrophils. Then, novel putative therapies for inflammatory and infectious diseases could be developed based on the characteristics presented by unsaturated fatty acids like OA. Finally, the purpose of this work was to review some of the modulatory effects of OA on inflammatory diseases and health, aiming at high lightening its potential role on the future establishment of novel therapeutic approaches for infections, inflammatory, immune, cardiovascular diseases or skin repair based on this fatty acid mainly found in the Mediterranean diet.
Toxicity of fatty acids on ECV-304 endothelial cells
Toxicology in Vitro, 2011
The effects of stearic (saturated) or oleic (monounsaturated) acids and their combination with x-3 and x-6 polyunsaturated fatty acids (PUFA) on death of endothelial cells (ECV-304 cell line) were investigated. We examined: loss of plasma membrane integrity, DNA fragmentation, accumulation of neutral lipids (NL) and release of reactive oxygen species (ROS). The fatty acids studied were: stearic (SA), oleic (OA), docosahexaenoic (DHA), eicosapentaenoic (EPA), linoleic (LA) and gamma-linolenic (cA) acids. SA at 150 lM induced cell death, did not lead to accumulation of NL and raised the release of ROS. x-3 PUFA decreased ROS production, increased NL content but did not protect against ECV-304 cell death induced by SA. x-6 PUFA inhibited SA-induced cell death, increased NL content and decreased ROS production. OA caused cell death but did not increase NL content and ROS production even at 300 lM. x-3 and x-6 FA associated with OA further increased cell death with no change in ROS production and NL content. Concluding, x-6 PUFA had a greater protective effect than x-3 PUFA on the deleterious effects caused by SA whereas OA had low cytotoxicity but, when associated with PUFA, presented marked toxic effects on ECV-304 endothelial cells.
Short-chain fatty acids modulate gene expression for vascular endothelial cell adhesion molecules
Nutrition, 2005
Objective: Leukocyte infiltration into the intestinal wall is central to the pathogenesis of tissue injury that occurs in patients with a variety of inflammatory bowel diseases. Migration of leukocytes from the intestinal circulation into bowel tissues is mediated by chemotactic substances and adhesion molecules (i.e., intercellular adhesion molecule-1 [ICAM-1] and E-selectin) on the surface of endothelial cells lining blood vessels. Short-chain fatty acids (SCFAs) derived from dietary fiber decrease inflammatory responses in colon cells. However, the effect of SCFAs on vascular adhesion molecules is unknown. We investigated the effects of SCFAs on vascular endothelial cell adhesion molecule expression. Methods: We assessed the effect of physiologically relevant concentrations of butyrate on expression of ICAM-1 protein and mRNA in cultures of human umbilical vein endothelial cells. We also assessed the effect of butyrate on levels of HLA-DR, E-selectin, vascular cell adhesion molecule-1, and endoglin. In additional experiments, we evaluated the effect of butyrate on ICAM-1 mRNA stability and the effect of valerate, isobutyrate, and propionate on ICAM-1 expression. The effect of butyrate on ICAM-1 expression was compared with that of trichostatin A, a specific inhibitor of histone deacetylase. Data were evaluated with Student's t tests or Tukey's multiple comparison tests, with P Ͻ 0.05 considered statistically significant. Results: Butyrate concentrations of 2.5 to 5 mM significantly increased endothelial expressions of ICAM-1 protein and mRNA. The effect of butyrate (5 mM) on ICAM-1 expression was time dependent, with significant increases in levels occurring after 16 h of incubation. Butyrate (5 mM) also increased expression of E-selectin but not of HLA-DR, vascular cell adhesion molecule-1, or endoglin. Isobutyrate had little effect on ICAM-1 expression, whereas valerate and propionate significantly increased expression of ICAM-1 but were weaker stimulants compared with butyrate. Butyrate (5 mM) did not alter stability of ICAM-1 mRNA. The effect of butyrate (5 mM) was comparable to that of trichostatin A. The stimulatory effect of butyrate on ICAM-1 expression was reversed after 48 h of butyrate withdrawal. Conclusions: Butyrate increases vascular endothelial expressions of ICAM-1 and E-selectin. We speculate that butyrate-induced effects on vascular adhesion molecules modulate gut inflammation. The role of SCFAs and fiber in the pathogenesis and modulation of gut inflammation in vivo requires further study. Nutrition 21 (2005) 740 -748 www.elsevier.com/locate/nut 0899-9007/05/$ -see front matter
Journal of Lipid Research, 1994
Lipid-derived free radicals were detected by electron paramagnetic resonance (EPR) spectrometry when cultured endothelial cells attached to Cytodex beads were exposed to ironinduced oxidant stress in the presence of the spin trap a-(4-pyridyl-l-oxide)-N-tert-butylnitrone (POBN). Radical adduct formation was enhanced greatly when the cells were supplemented during growth with polyunsaturated fatty acids. The largest EPR signal intensity was observed in cells enriched with docosahexaenoic acid (DHA) or eicosapentaenoic acid, but enhanced radical adduct production also occurred after exposure to arachidonic, a-linolenic, ylinolenic, or linoleic acids. Radical adduct formation increased as the DHA content of the cells increased and approached a maximum after only 6 h of exposure to DHA. Ascorbic acid, acting as a pro-oxidant, enhanced radical adduct formation in cells enriched with DHA. The EPR signal intensity was reduced when the cells were tested 6 h after replacement of the DHA-enriched medium with a medium containing 5-20 pM oleic acid, indicating that the increased endothelial responsiveness to oxidant stress is reversible. Likewise, when U937 monocytes enriched with DHA were exposed subsequently to 20 pM oleic acid, a 35-45% decrease in radical adduct formation also occurred. These findings suggest that the endothelium may become more susceptible to oxidative injury when it is exposed to elevated amounts of polyunsaturated fatty acids. However, the effect appears to be temporary. The protective action of oleic acid against oxidant stress is not confined to the endothelium; it applies to monocytes as wel1.
Trans-fatty acids induce pro-inflammatory responses and endothelial cell dysfunction
British Journal of Nutrition, 2008
Epidemiological data indicate that there is a strong association between intake of trans-18 : 2 fatty acids (TFA) and sudden cardiac death. There is little known about the mechanisms by which TFA exert harmful effects on the cardiovascular system. The present in vitro study is the first to demonstrate the effects of membrane-incorporated C18 : 2 TFA on human aortic endothelial cell (HAEC) function. Trans-18 : 2 fatty acids were incorporated to a greater extent (2-fold) in the phospholipid fraction of endothelial cells than that of cis-18 : 2; furthermore, these fatty acids were enriched to a similar extent in the TAG fraction. Flow cytometric analysis indicated that TFA treatment of HAEC significantly increased the expression of endothelial adhesion molecules, including intercellular adhesion molecule-1 (CD54) and vitronectin receptor (CD51/CD61). Incorporation of TFA into membranes increased HAEC adhesion to fibronectin- or vitronectin-coated plates by 1·5- to 2-fold, respectively....