Papel do desequilíbrio redox na patogenia da Síndrome metabólica: repercussões cardiometabólicas e na função arterial

Abstract

Introduction: The Metabolic Syndrome (MetS) is caracterized by a complex cluster of cardiometabolic disorders capable of augmenting the cardiovascular risk of its carriers. Although existing descriptions related to the association among such syndrome, oxidative stress and arterial function, many of the mechanisms involved in its pathophysiology still remain to be elucidated. Before these observations, the present study aimed to verify the redox balance profile in the pathogenesis of the MetS in human carriers, when compared to control ones, and its cardiometabolic and arterial function outcomes; Methods: For this observational study, 24 patients presenting with MetS were selected from the Federal University of Alagoas Teaching Hospital and 18 apparently healthy individuals from a private clinic, all of them age, sex, tobacco use and socioeconomic status-matched. The diagnosis for the cases was established according to the Harmonized version of the MetS (2009). During the clinical assessment, blood pressure levels and heart rate were obtained, followed by the anthropometric measurements: weight, height, waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR) and neck circumference (NC). After a 12-hour fasting period, venous blood samples were collected for general biochemical dosages [glycemic and lipid profile, AST, ALT, high-sensitive C-reactive protein (hs CRP), urea, creatinine and uric acid], as well as for the oxidative stress analyses (serum lipid peroxidation, SOD, catalase, arginase, glutathione peroxidase and myeloperoxidase enzymatic activities, as well as serum nitrite and hydrogen peroxide – H2O2 – concentrations). Estimated glomerular filtration rate (eGFR) was calculated base on the MDRD formula. The non-invasive assessment of the arterial function was performed using radial applanation tonometry, being obtained the augmentation index (AI); Results: Patients with MetS presented greater obesity indices than the respective controls (BMI: controls 26.69 ± 3.27 vs MetS 32.09 ± 7.10 kg.m-2, p < 0.01; WC: controls 87.89 ± 7.65 vs MetS 103.3 ± 13.96 cm, p < 0.0001; WHR: controls 0.83 ± 0.06 vs MetS 0.90 ± 0.09, p < 0.01; NC: 34.92 ± 3.24 vs MetS 37.46 ± 5.99 cm, p < 0.05), besides higher blood pressure levels and major loss of glycemic and lipid control. The case group presented higher levels for the markers of liver damage and uric acid, as well as reduced eGFR. Serum lipid peroxidation (controls 4.40 ± 0.65 vs MetS 7.99 ± 4.19 [MDA] mM.[Protein] mg.mL-1, p < 0.0001), erythrocyte SOD activity (controls 83.14 ± 57.27 vs MetS 128.60 ± 55.88 UI.mg Hb-1, p < 0.01), serum myeloperoxidase activity (controls 2.36 ± 0.33 vs MetS 2.80 ± 0.53 UI.mL-1.Protein mg.mL-1; p < 0.01) and H2O2 (controls 221.30 ± 181.70 vs MetS 501.00 ± 283.80 nmol.L-1; p < 0.001) were shown to be increased in the MetS group, with no statistically significant differences for the other considered enzymes, nitrite concentrations and the arterial assessment (AI) between the considered groups. Correlation analyses were more expressive between lipid peroxidation and obesity indices/biochemical profile; Conclusion: In patients with MetS, the greater indices of obesity and blood pressure were accompanied by a considerable loss of biochemical regulation compared to controls, although the specific pharmacological therapy in the case group. The lack of difference for the marker of arterial stiffness may indicate the probable influence of the current drug therapy. Furthermore, patients with MetS exhibited evident systemic redox imbalance compared to controls, with the probable participation of the MPO-H2O2 pathway as a contributor in the lipoperoxidation observed in individuals with MetS. Finally, the observed correlations point to the important role of oxidative stress in the maintenance of metabolic disturbances related to the MetS.