Abstract

Pharmaco-therapeutic strategies of atrial fibrillation (AF) are moderately effective and do not prevent AF onset and progression. Therefore, there is an urgent need to develop novel therapies. Previous studies revealed heat shock protein (HSP)-inducing compounds to mitigate AF onset and progression. Such an HSP inducing compound is L-glutamine. In the current study we investigate the effect of L-glutamine supplementation on serum HSP27 and HSP70 levels and metabolite levels in patients with AF patients (n = 21). Hereto, HSP27 and HSP70 levels were determined by ELISAs and metabolites with LC-mass spectrometry. HSP27 levels significantly decreased after 3-months of L-glutamine supplementation [540.39 (250.97–1315.63) to 380.69 (185.68–915.03), p = 0.004] and normalized to baseline levels after 6-months of L-glutamine supplementation [634.96 (139.57–3103.61), p < 0.001]. For HSP70, levels decreased after 3-months of L-glutamine supplementation [548.86 (31.50–1564.51) to 353.65 (110.58–752.50), p = 0.045] and remained low after 6-months of L-glutamine supplementation [309.30 (118.29–1744.19), p = 0.517]. Patients with high HSP27 levels at baseline showed normalization of several metabolites related to the carbohydrates, nucleotides, amino acids, vitamins and cofactors metabolic pathways after 3-months L-glutamine supplementation. In conclusion, L-glutamine supplementation reduces the serum levels of HSP27 and HSP70 within 3-months and normalizes metabolite levels. This knowledge may fuel future clinical studies on L-glutamine to improve cardioprotective effects that may attenuate AF episodes.

Highlights

  • Atrial fibrillation (AF) is a progressive, age-related disease affecting worldwide approximately33.5 million individuals and is regarded as one of the cardiovascular epidemics of the 21th century [1]

  • A strong correlation was found between the baseline level of HSP27 or HSP70 and the degree of reduction at 3-months of L-glutamine supplementation: patients of HSP27 or HSP70 and the degree of reduction at 3-months of L-glutamine supplementation: with a higher baseline level of HSP27 or HSP70 revealed a large reduction, whereas patients with a low patients with a higher baseline level of HSP27 or HSP70 revealed a large reduction, whereas patients

  • Our study reveals that the level of HSP27 significantly decreased after 3-months of

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Summary

Introduction

Atrial fibrillation (AF) is a progressive, age-related disease affecting worldwide approximately33.5 million individuals and is regarded as one of the cardiovascular epidemics of the 21th century [1]. Atrial fibrillation (AF) is a progressive, age-related disease affecting worldwide approximately. Treatment modalities for AF are only moderately effective and do not prevent AF onset and progression from recurrent intermittent episodes to permanent AF. Though invasive ablation therapy initially seemed promising in early stage AF, up to 50% of the AF patients with more persistent types of AF have recurrences within 1 year and require multiple procedures [3]. Cells 2020, 9, 1729 therapy of AF is even less effective, and its usage is limited by severe and potentially life-threatening side-effects. Main reason for AF therapy failure is that pharmaco-therapeutic strategies are not directed at mechanistic root causes of AF, which drive structural cardiomyocyte damage, mitochondrial dysfunction and electrical and contractile dysfunction of atrial cardiomyocytes [4,5]

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