Abnormalities in lysine degradation are involved in early cardiomyocyte hypertrophy development in pressure-overloaded rats

BMC Cardiovascular Disorders

Xiaojing Wu¹  Lanlan Tan²  Qi Zhou²  Jialing Liu²  Junhao Hu² 

[1] Cardiovascular Department of Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy, NO.1098 Xueyuan Street, Nanshan District, 518060, Shenzhen, People’s Republic of China;Cardiovascular Department of the Second Affiliated Hospital of Chongqing Medical University, NO.74 Linjiang Road, Yuzhong District, 400010, Chongqing, People’s Republic of China;

关键词: Cardiac hypertrophy;    Pressure overload;    Lysine degradation;    Metabolomics;    Nonenergetic metabolism;   

DOI  :  10.1186/s12872-021-02209-w

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY