Remodeling of myocardial energy and metabolic homeostasis in a sheep model of persistent atrial fibrillation
| Autor: | Yu-Wen Huang, Yan-Sheng Ding, Jihong Guo, Gang Li, Jiangbo Duan, Shandong Yu, Fei-Fei Liu, Lin Wu, Yanpeng Chu, Feng Ze, Wei Yang, Ying Chen, Cheng-Yu Wang, Xiaoyan Liu, Xuebin Li, Qi-Qiang Jie |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Citric Acid Cycle Biophysics Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Atrial Fibrillation medicine Animals Homeostasis Glycolysis Molecular Biology Mineralocorticoid Receptor Antagonists chemistry.chemical_classification Sheep Aldosterone inhibitor Myocardium Fatty acid Lipid metabolism Cell Biology Metabolism Phosphatidic acid Lipid Metabolism Amino acid Eplerenone Citric acid cycle Disease Models Animal 030104 developmental biology Endocrinology Glucose chemistry 030220 oncology & carcinogenesis Energy Metabolism Metabolic Networks and Pathways |
| Zdroj: | Biochemical and biophysical research communications. 517(1) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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