Abstract
BackgroundCardiomyocyte metabolism changes before cardiac remodeling, but its role in early cardiac hypertrophy detection remains unclear. This study investigated early changes in plasma metabolomics in a pressure-overload cardiac hypertrophy model induced by transverse aortic constriction (TAC).MethodsThe TAC model was constructed by partly ligating the aortic arch. Twelve Sprague–Dawley rats were randomly divided into the TAC group (n = 6) and sham group (n = 6). Three weeks after surgery, cardiac echocardiography was performed to assess cardiac remodeling and function. Hematoxylin/eosin (HE), Masson, and wheat germ agglutinin (WGA) stains were used to observe pathological changes. Plasma metabolites were detected by UPLC-QTOFMS and Q-TOFMS. Specific metabolites were screened by orthogonal partial least squares discriminant analysis (OPLS-DA). Metabolic pathways were characterized by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the predictive value of the screened metabolites was analyzed by receiver operating characteristic (ROC) curve analysis.ResultsThree weeks after surgery, the TAC and sham groups had similar left heart function and interventricular septum and diastolic left ventricular posterior wall thicknesses. However, on pathological examination, the cross-sectional area of cardiomyocytes and myocardial fibrosis severity were significantly elevated in TAC rats. OPLS-DA showed different metabolic patterns between the TAC and sham groups. Based on the criteria VIP > 1 and P < 0.05, 13 metabolites were screened out. KEGG analysis identified disrupted lysine degradation through the related metabolites 5-aminopentanoic acid, N6-acetyl-l-lysine, and l-lysine, with areas under the ROC curve (AUCs) of 0.917, 0.889, and 0.806, respectively, for predicting compensated cardiomyocyte hypertrophy.ConclusionDisruption of lysine degradation might be involved in early cardiac hypertrophy development, and related metabolites might be potential predictive and interventional targets for subclinical cardiomyocyte hypertrophy.
Highlights
Cardiomyocyte metabolism changes before cardiac remodeling, but its role in early cardiac hypertrophy detection remains unclear
They found that transverse aortic constriction (TAC)induced cardiac hypertrophy was characterized by a shift in energy metabolism toward a greater reliance on glycolysis
Establishment of the cardiac hypertrophy model Compared with rats in the sham group, rats in the TAC group had higher tail arterial pressure (158 ± 16.30 mmHg vs 132 ± 5.85 mmHg, n = 6, P < 0.01) 3 weeks after aortic constriction, while no significant difference was observed in heart rate or body weight
Summary
Cardiomyocyte metabolism changes before cardiac remodeling, but its role in early cardiac hypertrophy detection remains unclear. This study investigated early changes in plasma metabolomics in a pressure-overload cardiac hypertrophy model induced by transverse aortic constriction (TAC). Cardiac hypertrophy is a common pathological change in the pathogenesis and progression of multiple cardiovascular diseases, including hypertension, coronary artery disease, and valvular heart disease. Schnelle et al [9] studied glucose carbon metabolism in pressure-overload cardiac hypertrophy using an in vivo [U-13C] glucose labeling strategy. They found that transverse aortic constriction (TAC)induced cardiac hypertrophy was characterized by a shift in energy metabolism toward a greater reliance on glycolysis. Whether specific nonenergetic small-molecule metabolites might be involved in the early pathogenesis of cardiac hypertrophy is not clear
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