1. Remodeling of myocardial energy and metabolic homeostasis in a sheep model of persistent atrial fibrillation.
- Author
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Jie QQ, Li G, Duan JB, Li XB, Yang W, Chu YP, Yu SD, Liu XY, Wang CY, Liu FF, Ze F, Huang YW, Chen Y, Ding YS, Guo JH, and Wu L
- Subjects
- Animals, Atrial Fibrillation drug therapy, Atrial Fibrillation pathology, Citric Acid Cycle drug effects, Disease Models, Animal, Eplerenone therapeutic use, Glucose metabolism, Homeostasis drug effects, Lipid Metabolism drug effects, Male, Metabolic Networks and Pathways drug effects, Mineralocorticoid Receptor Antagonists therapeutic use, Myocardium pathology, Sheep, Atrial Fibrillation metabolism, Energy Metabolism drug effects, Myocardium metabolism
- Abstract
Background: Atrial fibrillation (AF) is the most common progressive cardiac arrhythmia and is often associated with rapid contraction in both atria and ventricles. The role of atrial energy and metabolic homeostasis in AF progression is under-investigated., Objectives: To determine the remodeling of energy metabolism during persistent AF and the effect of eplerenone (EPL), an aldosterone inhibitor, on metabolic homeostasis., Methods: A nonsustained atrial pacing sheep model was developed to simulate the progression of AF from paroxysmal to persistent. Metabolomic and proteomic analyses at termination of the experiment were used to analyze atrial tissues obtained from sheep in sham, sugar pill (SP) and EPL-treated groups., Results: Proteomic analysis indicated that compared to the sham group, in SP group, fatty acid (FA) synthesis, FA oxidation, tricarboxylic acid (TCA) cycle processes and amino acids (AAs) transport and metabolism were reduced, while glycolytic processes were increased. In metabolomic analysis, the levels of intermediate metabolites of the glycolytic pathways, including 2-phosphoglyceric acid (2 PG), 1,3-bisphosphoglyceric acid (1,3 PG), and pyruvate, HBP (uridine diphosphate-N-acetylglucosamine, UDP-GlcNAc), TCA (citrate) and AAs were greater while the levels of the majority of lipid classes, including phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylglycerol (PG), glycerophosphoglycerophosphates (PGP), glycerophosphoinositols (PI) and glycerophosphoserines (PS), were decreased in the atria of SP group than in those of sham group. EPL-pretreatment decreased the expression of glut4 and increased the content of acylcarnitines and lipids, such as lyso phospholipids, phospholipids and neutral lipids., Conclusion: In the metabolic remodeling during AF, glucose and lipid metabolism were up- and down-regulated, respectively, to sustain TCA cycle anaplerosis. EPL partialy reversed the metabolic shifting., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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