Avaliação da função vascular em modelo murino de aterosclerose tratado com lifepro, uma formulação nutracêutica composta por cepas de limosilactobacillus fermentum e polifenóis

Abstract

Atherosclerosis is one of the leading cardiovascular diseases. Hypercholesterolemia has been identified as the main atherogenic factor in humans, exacerbated by an unbalanced diet. Probiotics in combination with phenolic compounds have proven effective in reducing lipidemia in animals. The Federal University of Paraíba developed a new nutraceutical formulation by combining the probiotic Limosilactobacillus fermentum (strains 139, 263, 296) and the phenolic compounds quercetin and resveratrol (LifePro). This research aimed to investigate the vascular effects of the nutraceutical in apolipoprotein E knockout atherosclerotic mice (apoE-/- ) subjected to an atherogenic diet. Three groups were analyzed: control animals without genetic modification (wild type, WT); apoE-/- animals that received a vehicle, and apoE-/- animals that received the nutraceutical for eight weeks. At the end, the animals were euthanized to assess biochemical and inflammatory patterns, lipid deposition, and vascular reactivity in the aorta artery. The administration of the nutraceutical had a hypocholesterolemic effect, reducing cholesterol in treated apoE-/- animals (579±46 mg/dL##) compared to vehicle-treated apoE-/- animals (978±68 mg/dL**), but not in relation to the healthy control group (73±6 mg/dL). There was also a hypoglycemic effect in the treated group (249±16 mg/dL#) compared to the saline apoE-/- group (300±12 mg/dL). Triglycerides were also reduced in treated animals (145±18 mg/dL#* vs. apoE-/- saline 211±16 mg/dL**). The lipoprotein profile showed alterations in the apoE-/- vehicle group (HDL: 17±2 mg/dL** vs. WT 41±2 mg/dL and LDL: 159±21** mg/dL vs. WT: 5±0.7 mg/dL), while HDL and LDL levels were not altered by the treatment. On the other hand, VLDL was reduced in the treated group (503±62 mg/dL#*) compared to the saline group (776±46 mg/dL##), both differing from healthy animals (28±3 mg/dL). The treatment did not influence food intake or weight. Oxidative stress was higher in the apoE-/- saline group (30±1 mmol/mL vs. WT 13±1 mmol/mL), and LifePro reduced MDA concentrations (14±2### mmol/mL). Regarding vascular reactivity, the apoE-/- vehicle group showed increased vasoconstriction in response to phenylephrine (Rmax: 88±7%) compared to the healthy control group (Rmax: 70±3%) and impaired endothelium-dependent relaxation (apoE-/- vehicle Rmax: 48±6% vs. WT Rmax: 89±5%), highlighting endothelial dysfunction in this group. The nutraceutical improved endothelial dysfunction by reducing vasoconstrictive behavior (apoE-/- treated Rmax: 50±3%##) and increasing relaxation in response to acetylcholine (apoE-/- treated Rmax: 107±12%##). The treatment restored NO-mediated relaxation and reduced the impact of oxidative stress in organ baths. Concerning the inflammatory profile, TNF (18±1 pg/mL vs. 7±1 pg/mL) and MCP-1 (145±12** pg/mL vs. 77±8 pg/mL) cytokines were higher in the apoE-/- saline group compared to WT, while IL-6 and IL-10 levels did not show alterations between groups. The treatment did not modify cytokine levels. Lipid deposition in the aortic arch was accentuated in apoE-/- saline animals (45±2%), while treatment (27±2%##) reduced plaque percentage by 1.2 times. Thus, we suggest that the treatment proved effective in a murine model of atherosclerosis.