Effects of ω-3 PUFAs supplementation on myocardial function and oxidative stress markers in typical Rett syndrome

Abstract

Rett syndrome (RTT) is a devastating neurodevelopmental disorder with a 300-fold increased risk rate for sudden cardiac death. A subclinical myocardial biventricular dysfunction has been recently reported in RTT by our group and found to be associated with an enhanced oxidative stress (OS) status. Here, we tested the effects of the naturally occurring antioxidants ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on echocardiographic parameters and systemic OS markers in a population of RTT patients with the typical clinical form. A total of 66 RTT girls were evaluated, half of whom being treated for 12 months with a dietary supplementation of ω-3 PUFAs at high dosage (docosahexaenoic acid ~71.9 ± 13.9 mg/kg b.w./day plus eicosapentaenoic acid ~115.5 ± 22.4 mg/kg b.w./day) versus the remaining half untreated population. Echocardiographic systolic longitudinal parameters of both ventricles, but not biventricular diastolic measures, improved following ω-3 PUFAs supplementation, with a parallel decrease in the OS markers levels. No significant changes in the examined echocardiographic parameters nor in the OS markers were detectable in the untreated RTT population. Our data indicate that ω-3 PUFAs are able to improve the biventricular myocardial systolic function in RTT and that this functional gain is partially mediated through a regulation of the redox balance.

Figure 1

Dietary ω-3 PUFAs supplementation for 12 months significantly improves biventricular systolic longitudinal parameters in girls with typical Rett syndrome. MAPSE: mitral annular plane systolic excursion; TAPSE: tricuspid annular plane systolic excursion; S′_lat: peak systolic velocity of lateral mitral annulus; S′_sep: peak systolic velocity of septal mitral annulus; S′_RV: peak systolic velocity of tricuspid annulus of right ventricle; PASP: pulmonary arterial systolic pressure; E/A: ratio between peak early diastolic mitral flow (E) and peak late diastolic mitral flow (A); E′_lat: peak early diastolic velocity of lateral mitral annulus; E′_RV: peak early diastolic velocity of tricuspid annulus of right ventricle; E/E′_lat: this ratio indirectly estimates left ventricle end-diastolic filling pressure.

Figure 2

Oxidative stress markers levels (NPBI, plasma F₂-IsoPs, and F₄-NeuroPs) are significantly reduced in the ω-3 PUFAs supplemented Rett population, as compared to basal values (Panels (a)–(d)). Conversely, no significant changes were observed for 4-HNE PAs values (Panel (e)). *denotes P value < 0.05. NPBI: non protein-bound iron; F₂-IsoPs: plasma free F₂-isoprostanes; F₄-NeuroPs: plasma free F₄-neuroprostanes; 4-HNE protein adducts: 4-hydroxynonenal protein adducts; mo.s: months.