Wafa Kharroubi

Correlation of trans fatty acids with the severity of coronary artery disease lesions

BackgroundNutritional choices, which include the source of dietary fatty acids (FA), have an important significant impact on coronary artery disease (CAD). We aimed to determine on patients with CAD the relationships between Trans fatty acids (Trans FA) and different CAD associated parameters such as inflammatory and oxidative stress parameters in addition to Gensini score as a vascular severity index.MethodsFatty acid profiles were established by gas chromatography from 111 CAD patients compared to 120 age-matched control group. Lipid peroxidation biomarkers, oxidative stress, inflammatory parameters and Gensini score were studied.ResultsOur study showed a significant decrease of the antioxidant parameters levels such as erythrocyte glutathione peroxydase (GPx) and superoxide dismutase (SOD) activities, plasma antioxidant status (FRAP) and thiol (SH) groups in CAD patients. On the other hand, catalase activity, conjugated dienes and malondialdehyde were increased. Plasmatic and erythrocyte Trans FA were also increased in CAD patients compared to controls. Furthermore, divergent associations of these Trans FA accumulations were observed with low-density lipoprotein-cholesterol/ high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio, Apolipoprotein B (ApoB), lipid peroxidation parameters, high-sensitivity C Reactive Protein (hs-CRP), Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and Gensini score. Especially, elaidic acid (C18:1 trans 9), trans C18:2 isomers and trans 11 eicosanoic acid are correlated with these parameters. Trans FA are also associated with oxidative stress, confirmed by a positive correlation between C20:1 trans 11 and GPx in erythrocytes.ConclusionsHigh level of Trans FA was highly associated with the induction of inflammation, oxidative stress and lipoperoxidation which appear to be based on the vascular severity and might be of interest to assess the stage and progression of atherosclerosis. The measurement of these Trans FA would be of great value for the screening of lipid metabolism disorders in CAD patients.

Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate

The treatment of microglial BV-2 cells with sodium arsenate (As(V): 0.1-400μmol/L - 48hr) induces a dose-dependent response. The neurotoxic effects of high concentrations of As(V) (100, 200 and 400μmol/L) are characterized by increased levels of mitochondrial complexes I, II, and IV followed by increased superoxide anion generation. Moreover, As(V) triggers an apoptotic mode of cell death, demonstrated by an apoptotic SubG1 peak, associated with an alteration of plasma membrane integrity. There is also a decrease in transmembrane mitochondrial potential and mitochondrial adenosine triphosphate ATP. It is therefore tempting to speculate that As(V) triggers mitochondrial dysfunction, which may lead to defective oxidative phosphorylation subsequently causing mitochondrial oxidative damage, which in turn induces an apoptotic mode of cell death.

Protective effects of bezafibrate against elaidic acid-induced accumulation of lipid droplets in monocytic cells

Some factors related to diet, such as trans fatty acids (TFA), are known to be involved in the progression of atherosclerosis in humans. Thus, the aim of our study was (i) to evaluate the effects of three dietary free fatty acids (FFA) (elaidic (EA), oleic (OA) and palmitic acid (PA)) on U937 human monocytes, and (ii) to study the eventual benefits of bezafibrate (BZF), a pan-agonist for PPAR isoforms (α, γ and δ) in U937 cells treated with FFA. Morphologic and functional changes were investigated by microscopic and flow cytometric methods. Cellular lipid content, lipid droplets and FA composition were identified and studied. All analyses were also realized in association with or without BZF. Contrary to OA and PA, EA slightly induced both propidium iodide-positive cells and mitochondrial depolarization. In addition, in contrast to OA and PA, EA induced only a slight increase in superoxide anion production. However, EA and OA promoted cytoplasmic lipid droplets accumulation. Only EA and OA significantly increased CD36 expression. It is noteworthy that BZF had a more or less pronounced protective effect against EA-, OA- and PA-induced side effects: BZF attenuated the impaired cell viability and inflammatory response, decreased superoxide anion production and prevented the accumulation of neutral and polar lipids. The effects were less pronounced with OA and PA than with EA. Altogether, our data revealed a benefit of BZF on the side effects induced especially with EA. It may thus be of interest in preventing the early stages of atherosclerotic plaque formation.

Induction by arsenate of cell-type-specific cytotoxic effects in nerve and hepatoma cells

The aim of the study was to compare the effect of sodium arsenate (AsV) on two different cell types: 158N murine oligodendrocytes and HepG2 human hepatoma cells. Exposure of 158N cells to AsV (0.1–400 µM; 48 h) induced a biphasic cytoxic effect defined as hormesis. Thus, low concentrations of AsV stimulate cell proliferation, as shown by phase-contrast microscopy, cell counting with trypan blue, and crystal violet assay, whereas high concentrations induce cell death associated with a loss of cell adhesion. These side effects were confirmed by staining with propidium iodide and cell cycle analysis, characterized by the presence of a subG1 peak, a criterion of apoptosis. The effects of AsV on mitochondrial function, as determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, the measurement of mitochondrial transmembrane potential with 3,3′-dihexyloxacarbocyanine iodide, and the rate of mitochondrial adenosine triphosphate confirm the impact of AsV on the mitochondria. In contrast to 158N cells, HepG2 cells were susceptible to all AsV concentrations as shown by microscopic observations, by counting with trypan blue. However, no alteration is noted in the cell membrane integrity, which indicated an apoptotic mode of cell death, and this side effect is confirmed by the cycle analysis, which revealed a subG1 peak. Of note, there was a loss of MTT, suggesting that AsV induces mitochondrial complex II dysfunction. Altogether, our data show that the cytotoxic characteristics of AsV depend on the cell type considered.

Consumption of Oxidized and Partially Hydrogenated Oils Differentially Induces Trans-Fatty Acids Incorporation in Rats' Heart and Dyslipidemia

Objectives: A direct effect of process-induced trans-fatty acids (TFAs) on nonalcoholic fatty liver disease (NAFLD) as a cardiovascular disease (CVD) risk factor has previously been shown. We hypothesized that TFAs directly induced CVD. This article describes an investigation of the association between TFAs, provided by the consumption of oxidized soybean oil and margarine, and plasma lipid profiles, coronary artery lesions, and coronary fatty acids distribution in rats. Male rats were fed a standard chow or high-fat diet containing different TFA levels ranging from <1%, <2%, and >2% of total fat in fresh soybean oil, oxidized soybean oil, and margarine, respectively, for 4 weeks. Results: The results indicated that the high-fat diets differently changed the plasma lipid profiles by significantlt increasing triglycerides, total cholesterol, low-density lipoprotein cholesterol, and the ratio of low-density to high-density lipoprotein cholesterol compared to control rats. Compared to fresh soybean oil, oxidized oil further increased plasma lipid markers. The strongest inflammatory effect was induced by margarine, which contains the highest level of TFAs, or 2% of total fat. Total TFAs in the heart of the margarine-fed group were increased by 4.7 regarding to control and by 2.17 and 2.6 relative to groups receiving oxidized and fresh oil, respectively. Increased TFAs consumption was associated with increased histological aspects of atherosclerotic lesions in a dose-dependent manner. Conclusion: In conclusion, process-induced TFAs cause changes including proatherogenic plasma lipid markers, heart fatty acid profiles, and coronary artery histology depending on the TFA level in the supplemented fat and therefore on the type of technological process used.

Identification of long and very long chain fatty acids, plasmalogen-C16:0 and phytanic acid as new lipid biomarkers in Tunisian coronary artery disease patients

Long and very long chain fatty acids (LCFAs and VLCFAs) may play an active role in coronary artery diseases (CAD) etiology. Our aim was to evaluate the associations between LCPUFAs (C20:4n-6; C20:5n-3 and C22:6n-3) and VLCSFAs (C22:0, C24:0; and C26:0), as well as markers of peroxisomal integrity evaluated by phytanic acid and plasmalogen-C16:0 (PL-C16:0) in addition to the markers of lipid peroxidation (malondialdehyde [MDA] and conjugated dienes [CD]) and inflammation (high sensitivity C-reactive protein [hs-CRP]) with vascular severity evaluated by Gensini score in order to determine their possible effects on CAD in Tunisian population. Lipidomic strategy based on GC/MS-SIM was used to quantify LCPUFAs, VLCSFAs, and PL-C16:0 in red blood cells of CAD patients, non-CAD patients, and controls. We observed a significant increase in phytanic acid, PL-C16:0 and VLCFAs, particularly C26:0, in CAD group compared to controls. Further our findings showed positive correlations of C26:0 with MDA and with vascular severity score (Gensini score). In addition, a significant negative correlation was shown between hs-CRP and C22:6 n-3 (r=-0.297; p=0.002) and a significant positive association was observed between hs-CRP and C20:4 n-6 levels (r=0.196; p=0.039). Our results show changes in LCPUFAs and VLCSFAs concentrations in RBC among study groups, and suggest alterations in fatty acids metabolism regulated by elongase and desaturase enzymes. The positive correlations of C20:4n-6 and the negative correlations of C22:6n-3, simultaneously with Gensini score and hs-CRP, suggest a link of both inflammation and vascular severity complication of CAD with LCPUFAs and VLCSFAs. Induction of lipid oxidation, can be one of the outcomes of LCFAs and VLCFAs accumulation in vascular tissues and, thus, playing an important role in the pathogenesis of atherosclerosis. Quantification of LCPUFAs and VLCSFAs, phytanic acid and PL-C16:0 simultaneously, would be of great value for the screening of peroxisomal disorders in vascular tissue of CAD patients.