RESUMEN
High-density lipoproteins (HDLs) are known to enhance vascular function through different mechanisms, including the delivery of functional lipids to endothelial cells. Therefore, we hypothesized that omega-3 (n-3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of HDLs would improve the beneficial vascular effects of these lipoproteins. To explore this hypothesis, we performed a placebo-controlled crossover clinical trial in 18 hypertriglyceridemic patients without clinical symptoms of coronary heart disease who received highly purified EPA 460 mg and DHA 380 mg, twice a day for 5 weeks or placebo. After 5 weeks of treatment, patients followed a 4-week washout period before crossover. HDLs were isolated using sequential ultracentrifugation for characterization and determination of fatty acid content. Our results showed that n-3 supplementation induced a significant decrease in body mass index, waist circumference as well as triglycerides and HDL-triglyceride plasma concentrations, whilst HDL-cholesterol and HDL-phospholipids significantly increased. On the other hand, HDL, EPA, and DHA content increased by 131% and 62%, respectively, whereas 3 omega-6 fatty acids significantly decreased in HDL structures. In addition, the EPA-to-arachidonic acid (AA) ratio increased more than twice within HDLs suggesting an improvement in their anti-inflammatory properties. All HDL-fatty acid modifications did not affect the size distribution or the stability of these lipoproteins and were concomitant with a significant increase in endothelial function assessed using a flow-mediated dilatation test (FMD) after n-3 supplementation. However, endothelial function was not improved in vitro using a model of rat aortic rings co-incubated with HDLs before or after treatment with n-3. These results suggest a beneficial effect of n-3 on endothelial function through a mechanism independent of HDL composition. In conclusion, we demonstrated that EPA and DHA supplementation for 5 weeks improved vascular function in hypertriglyceridemic patients, and induced enrichment of HDLs with EPA and DHA to the detriment of some n-6 fatty acids. The significant increase in the EPA-to-AA ratio in HDLs is indicative of a more anti-inflammatory profile of these lipoproteins.
Asunto(s)
Ácidos Grasos Omega-3 , Animales , Ratas , Ácido Araquidónico , Estudios Cruzados , Suplementos Dietéticos , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/farmacología , Células Endoteliales , Ácidos Grasos , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Lipoproteínas , Triglicéridos , HumanosRESUMEN
BACKGROUND: Postprandial triglyceridemia may transitory affect the structure of HDL subclasses and probably their antiatherogenic properties but little is known in this field. We analyzed the HDL subclasses lipid content along postprandial period. METHODS: Fifteen metabolic syndrome (MS) patients and 15 healthy controls were enrolled. HDL were isolated from plasma samples obtained at fasting and every 2-h up to 8-h, after a 75-g fat meal. Cholesterol (C), triglycerides (TAG), and phospholipid (Ph) plasma concentrations of five HDL subclasses were determined by densitometry of electrophoresis gels enzymatically stained. RESULTS: The increase of postprandial triglyceridemia expressed as the incremental area under the curve (iAUC) was twice in MS patients than in controls. Only large HDL2b-TAG were higher in MS than controls at 4, 6 and 8h after meal intake, whereas cholesterol of HDL2a, 3a and 3b were lower at 8h. HDL size distribution shifted towards large HDL and HDL3a-, 3b- and 3c-subclasses had a lower content of cholesterol (estimated by the C-to-Ph ratio) in subjects whose iAUC>289.5mgh/dl (n=15) in comparison with those subjects with iAUC below this cutoff point (n=15), independently of the MS status and fasting TAG. Triglycerides content of HDL subclasses changed only discreetly along the postprandial period, whereas paraoxonase-1 remained unchanged. CONCLUSIONS: A high postprandial triglyceridemia conditions the shift of HDL size distribution towards large particles and the decrease of cholesterol in HDL3 subclasses. These data demonstrate that postprandial hypertriglyceridemia contributes to a transitory hypoalphalipoproteinemia that may increase the risk of cardiovascular disease.