Correlation between increased atrial expression of genes related to fatty acid metabolism and autophagy in patients with chronic atrial fibrillation

Abstract

Atrial metabolic disturbance contributes to the onset and development of atrial fibrillation (AF). Autophagy plays a role in maintaining the cellular energy balance. We examined whether atrial gene expressions related to fatty acid metabolism and autophagy are altered in chronic AF and whether they are related to each other. Right atrial tissue was obtained during heart surgery from 51 patients with sinus rhythm (SR, n = 38) or chronic AF (n = 13). Preoperative fasting serum free-fatty-acid levels were significantly higher in the AF patients. The atrial gene expression of fatty acid binding protein 3 (FABP3), which is involved in the cells' fatty acid uptake and intracellular fatty acid transport, was significantly increased in AF patients compared to SR patients; in the SR patients it was positively correlated with the right atrial diameter and intra-atrial electromechanical delay (EMD), parameters of structural and electrical atrial remodeling that were evaluated by an echocardiography. In contrast, the two groups' atrial contents of diacylglycerol (DAG), a toxic fatty acid metabolite, were comparable. Importantly, the atrial gene expression of microtubule-associated protein light chain 3 (LC3) was significantly increased in AF patients, and autophagy-related genes including LC3 were positively correlated with the atrial expression of FABP3. In conclusion, in chronic AF patients, the atrial expression of FABP3 was upregulated in association with autophagy-related genes without altered atrial DAG content. Our findings may support the hypothesis that dysregulated cardiac fatty acid metabolism contributes to the progression of AF and induction of autophagy has a cardioprotective effect against cardiac lipotoxicity in chronic AF.

Small-Molecule Integrated Stress Response Inhibitor Reduces Susceptibility to Postinfarct Atrial Fibrillation in Rats via the Inhibition of Integrated Stress Responses

“…Previous studies have showed that the autophagy-related protein LC3 increased in the left atrium of human chronic AF (Shingu et al, 2020) and AF animals (Wiersma et al, 2017;Yuan et al, 2018). Our results showed that MI promoted LC3 expression in LA which was partly reversed by ISRIB treatment.…”

[Retracted] Multiomics Analysis of Genetics and Epigenetics Reveals Pathogenesis and Therapeutic Targets for Atrial Fibrillation

“…As previous studies, serum fatty acid binding proteins have been considered as potential biomarkers for AF [ 29 ]. Fatty acid metabolism-related genes are distinctly correlated to autophagy among patients with chronic AF [ 30 ]. Hence, it is of importance to further probe into the functions of these genes in the fatty acid metabolic process.…”

Impaired Relaxation and Reduced Lusitropic Reserve in Atrial Myocardium in the Obese Patients

“…Most (but not all) studies investigating the relationship between FABP3 and atrial remodeling have shown evidence for a contribution of FABP3 to the atrial remodeling and AF based on FABP3 plasma levels or tissue messenger RNA (mRNA) (14)(15)(16)(17). From a mechanistic perspective, the protein concentration of FABP3 in the RA may be better suited to reflect the correlation between FABP3 regulation and RA function.…”

“…Fatty acid-binding protein 3 (FABP3) is an intracellular FA carrier, which has been evaluated as a biomarker of atrial maladaptive remodeling in patients with metabolic disease (12,13). Correlation of the plasma levels and genetic expression of FABP3 with atriomyopathy suggest a relation between FABP3 expression in the atrial tissue and atrial function; however, this has not yet been explored (14)(15)(16)(17).…”