Resveratrol Improves Heart Function by Moderating Inflammatory Processes in Patients with Systolic Heart Failure

Abstract

The effects of resveratrol (RES) in heart failure have already been evaluated in animal models; however, in human clinical trials, they have not been confirmed yet. The aim of this study was to assess the effects of resveratrol treatment in systolic heart failure patients (heart failure with reduced ejection fraction or HFrEF). In this human clinical trial, 60 outpatients with NYHA (New York Heart Association) class II-III HFrEF were enrolled and randomized into two groups: receiving either 100-mg resveratrol daily or placebo for three months. At the beginning and at the end of the study echocardiography, a six-minute walk test, spirometry, quality of life questionnaire, lab test and RNA profile analysis were performed. The systolic and diastolic left ventricular function, as well as the global longitudinal strain, were improved significantly in the resveratrol-treated group (RES). Exercise capacity, ventilation parameters and quality of life also improved significantly in the RES group. In parallel, the cardiac biomarker levels (N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and galectin-3) decreased in the treated group. The level of inflammatory cytokines decreased significantly after RES supplementation, as a consequence of the decreased expression level of leucocyte electron transport chain proteins. The main findings of our trial are that RES treatment added to the standard heart failure therapy improved heart function and the clinical condition by moderating the inflammatory processes in patients with HFrEF.

Keywords: echocardiography; heart failure; inflammation; oxidative stress; resveratrol.

Figure 1

Study design. HFrEF: heart failure with reduced ejection fraction, N: number of patients and RES: resveratrol.

Figure 2

Effect of resveratrol on inflammatory cytokines in heart failure patients. Values are expressed as mean ± SEM. * p < 0.05 vs. placebo group at the 3rd month. Baseline: measured values at randomization in resveratrol or in placebo group and 3rd month: patients treated with resveratrol or placebo for 3 months. IL: interleukin.

Figure 3

Effects of resveratrol on the biomarkers of heart failure. Values are expressed as mean ± SEM. * p< 0.05 vs. placebo group at the 3rd month. Baseline: measured values at randomization in the resveratrol or in the placebo group and 3rd month: patients treated with resveratrol or placebo for 3 months. NT-proBNP: N-terminal prohormone of brain natriuretic.

Figure 4

The effect of resveratrol on the left ventricular systolic and diastolic functions. Values are expressed as mean ± SEM. * p < 0.05, 3rd month values of the resveratrol group compared to the baseline values. ** p < 0.01, 3rd month values of the resveratrol group compared to the baseline values. # p < 0.05, resveratrol vs. placebo group at the 3rd month. Baseline: measured values at randomization in the resveratrol or in the placebo group; 3rd month: patients treated with resveratrol or placebo for 3 months. E: early diastolic ventricular filling velocity, E’: early diastolic mitral annular velocity, EF: ejection fraction and GLS: global longitudinal strain of the left ventricle.

Figure 5

(A) Summary of the canonical pathways impacted by the differentially expressed genes (DEGs) due to the resveratrol treatment (n = 7). Coloring of the bars represents the predicted activation state of the given pathway based on Z-score calculations applied on the differential expression of the genes in our study, included in the given canonical pathway. (B) Resveratrol supplementation induced expressional alterations in human leukocytes. Heat map visualizing the expression values of the differentially expressed genes (the most demonstrative 3 patients) significant in the resveratrol-treated patients. Hierarchical clustering was conducted on Euclidean distances and complete linkages. (C) The effect of RES on electron transport chains (ETC) in leukocytes. The canonical pathway of oxidative phosphorylation (generated by the IPA /Ingenuity Pathway Analysis/ program) depicting (green) only the members of ETC complexes demonstrating suppressed expression due to the resveratrol treatment. ADP: adenosine diphosphate, ATP: adenosine triphosphate, CoQ: coenzyme Q, MT-ATP6: gene of mitochondrial ATP synthase, NAD: nicotinamide adenine dinucleotide, ND: NADH dehydrogenase and CYT: cytochrome.