Apple polyphenols decrease endothelial dysfunction and atherosclerosis after chronic Western diet in a ApoE mouse model

Apple polyphenols decrease endothelial dysfunction and atherosclerosis after chronic Western diet in a ApoE mouse model

Topic 2 - Atherosclerosis, thrombosis, hemostasis — A was calculated. For platelet activation assays, human or rat washed platelets were incubated for...

158KB Sizes 0 Downloads 35 Views

Topic 2 - Atherosclerosis, thrombosis, hemostasis — A was calculated. For platelet activation assays, human or rat washed platelets were incubated for 60 min with both alloys before measuring their reactivity to platelet agonists by flow cytometry, using CD62P and activated ␣2b␤3 antibodies. In addition, phosphorylation of PKC substrates was evaluated by western blot. Results No significant red cells haemolysis was induced by both alloys (0.5 and 0.3% respectively). In addition, Co-Cr alloy did not affect CD62P exposure and ␣2b␤3 activation at platelet surface upon thrombin (0.03 to 0.3 U/ml) stimulation. In contrast, Fe alloy completely abolished their response to the agonist. A drastic inhibition of the phosphorylation state of PKC substrates was also observed after activation with thrombin, collagen (1.25 to 5 ␮g/ml) and ADP (0.1 to 10 ␮M). Since similar inhibitory effects were obtained when using a conditioned-reaction medium previously incubated with this Fe alloy, we postulate that its biocorrosion might release components counteracting platelet activation. Conclusion The Fe-based resorbable scaffold displays antithrombogenic properties and is a promising platform for nextgeneration stent technologies. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2018.02.011 400

An administration of polyphenols improves endothelial function and the inflammatory status in dogs A. Moinard ∗ , V. Leray ONIRIS, La Limouzinière, France ∗ Corresponding author. E-mail address: [email protected] (A. Moinard) Introduction In humans, after a hyperlipidemic meal, an alteration of the endothelial function has been described, that occurred simultaneously with the peak of plasma triglycerides and markers of oxidative stress and inflammation. Polyphenols intake, especially flavonoids, has been described to exert beneficial effects on cardiovascular function. However, the effect of polyphenols endothelial function, inflammation and oxydative stress in postprandial state is unknown in dogs. Objective Our aim was to assess the effects of a single administration of polyphenols extracted from grape seed on endothelial function inflammatory status and oxydative stress in postprandial state in dogs. Method Ten healthy adult beagles were enrolled in this Latin-square study. Dogs received 4 meals separates of a 1-week wash-out period a standard meal, a standard meal and polyphenols, a hyperlipidic meal (a standard meal and sunfloweroil and a hyperlipidic meal and polyphenols. Flow mediated dilatation (FMD), triglycerides, total cholesterol, HDL-Cholesterol, Malondialdehyde, CRP, serumamyloid A, Haptoglobine were assayed before, 2 and 4 h after the meal. Results FMD was higher 4 h after standard meal with polyphenols compared to the standard meal, but was unchanged after the hyperlipidic meal and polyphenols compared to the hyperlipidic meal. The plasma concentration of haptoglobin was higher after a hyperlipidic meal compared to a standard meal but not after a hyperlipidic meal and polyphenols. Conclusion At the dose we used, a single administration of polyphenols improved endothelial function after the standard meal but seemed to be inefficient to counterbalance the effects of the hyperlipidic meal. Moreover, the polyphenols intake abolished

181 the higher haptoglobine concentration measured after the high-fat meal. Our study suggests that a single administration of polyphenols could induce an upgrade of postprandial inflammation associated with an improvement in endothelial function in dogs. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2018.02.012 157

Apple polyphenols decrease endothelial dysfunction and atherosclerosis after chronic Western diet in a ApoE mouse model G. Bolea 1,2,∗ , C. Philouze 2 , M. Dubois 2 , A. Humberclaude 2 , C. Ginies 1 , C. Arnaud 3 , G. Meyer 2 , C. Dufour 1 1 UMR408 SQPOV ‘‘safety and quality of plant products’’, INRA, university of Avignon, Avignon, France 2 EA4278 LaPEC ‘‘laboratory of cardiovascular pharm-ecology’’, university of Avignon, Avignon, France 3 INSERM U1042 ‘‘cardiovascular & respiratory pathophysiology and hypoxia’’, university of Grenoble, Grenoble, France ∗ Corresponding author. E-mail address: [email protected] (G. Bolea) Introduction Atherosclerosis is a multifactorial disease and a leading cause of mortality in industrialized countries associated with endothelial dysfunction, oxidative stress and inflammation, which contribute to lesion formation, plaque rupture and thrombosis. One of the main risk factors for this pathology is the pro-oxidant Western diet rich in ␻-6 polyunsaturated fatty acids (␻-6PUFA) which are sensitive to oxidation by heme iron of red meat in the gastrointestinal tract. This oxidation may increase the 4-hydroxy2-nonenal (4-HNE) formation, a specific genotoxic and cytotoxic aldehyde generated from ␻-6PUFA. Moreover, coupling of 4-HNE to LDL is a key step in atherosclerosis development. By contrast, a diet rich in procyanidins (PCs) (polyphenols, flavonoid) is known to reduce oxidative stress as well as coronary artery disease. Objective Evaluate chronic pro-oxidant Western diet effects on atherosclerosis development and vascular function in an ApoE−/− mice model and the potential antioxidant capacity of PCs. Method ApoE−/− mice were fed with: high-fat/red meat; highfat/␻-6PUFA/red meat; high-fat/␻-6PUFA/red meat supplemented with apple puree (0.06% eq. polyphenols) or a phenolic extract for 12 weeks. Results No difference was evidenced regarding insulin resistance or obesity development. However, we observed that lipid oxidation worsens endothelial dysfunction (62% vs. 75% maximal relaxation) compared to the high-fat diet rich in saturated fatty acids. This alteration of the endothelium was associated with an increase of arterial pressure and atheromatous plaque formation (136 mm2 vs. 166 mm2 ). Interestingly, both polyphenol supplementations prevented the exacerbation of endothelial function and atherosclerosis impairments. Conclusion Apple PCs may limit the formation of absorbable lipid oxidation products such as 4-HNE during digestion and consequently protect vascular function. The reintroduction of PC-rich fruits into our diet could have a health benefit. Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.acvdsp.2018.02.013