Correction of endothelial dysfunction in experimental metabolic syndrome with statins and polyphenol concentrates

Abstract

Endothelial dysfunction is one of the key pathogenetic factors that develop and progress in the context of metabolic syndrome. Due to the global prevalence of metabolic syndrome and its consequences, the search for and development of correction methods targeting the main pathogenetic links continues today.

Objective. To demonstrate the feasibility of using statins and polyphenol concentrates as effective treatments for endothelial dysfunction in experimental metabolic syndrome.

Methods. The study was conducted on 90 male Wistar albino rats weighing 150–200 g. Animals in the experimental group (n = 80) were fed solid food supplemented with a 60% fructose solution (modeling metabolic syndrome – MS) for 24 weeks, while animals in the control group (n = 10) were kept on a standard diet with free access to food and water. Starting from the 14th week of the experiment, rosuvastatin was added to the diet of one of the experimental group subgroups (n = 25), a concentrate of grapevine polyphenols was added to the diet of the other experimental subgroup (n = 25), and the remaining animals (n = 30) with MS did not undergo dietary correction. The development of MS was assessed by measuring body circumference, body weight, and glycemia levels. Endothelial dysfunction was assessed using enzyme-linked immunosorbent assay (ELISA) by comparing such parameters as the content of nitric oxide synthase and nitric oxide itself (eNOS and NO), endothelin-1 (ET-1), vascular growth factor (VEGF-A) in venous blood, and the level of systemic inflammation was reflected by C-reactive protein (CRP) and adiponectin.

Results. In the course of the experiment in animals, the development of MS was accompanied by a reliable decrease in the concentrations of VEGF-A by 72%, NO by 71%, eNOS by 10% and adiponectin by 21% (p = 0.001), as well as an increase in the level of ET-1 by 430% and CRP by 7.8% (p = 0.001). Correction with polyphenols normalizes the concentration of eNOS by 29% and NO by 35% (p = 0.002). The use of rosuvastatin led to an increase in eNOS compared to the MS group by only 23%, and NO by 12%. The use of polyphenols demonstrated a twofold (p = 0.008) decrease in ET-1, and the use of rosuvastatin blocked the growth to control values (p = 0.009). The applied correction methods had a minor impact on the increase in VEGF-A, with polyphenols increasing its concentration by 20% (p = 0.08), while rosuvastatin had no effect on its normalization (p = 0.002). This intervention also affected inflammatory markers: a 15% decrease in CRP and a 68% increase in adiponectin, relative to values in individuals with MS.

Conclusion. The methods used for nutritional correction of MS confirmed the pleiotropic effects of statins and polyphenols, among which the anti-inflammatory and angioprotective effects play a key role. Therefore, a more pronounced corrective role of polyphenols in nitric oxide markers was noted compared to statins. Therefore, further studies will evaluate the effectiveness of combination therapy with polyphenols and lipid-lowering drugs from the statin group to enhance the effectiveness of correcting metabolic changes.