Abnormalities in lysine degradation are involved in the regulation of early stage compensated cardiac hypertrophy in pressure-overloaded rats

Background Cardiomyocyte metabolism changes before cardiac remodeling. However, its role in early detection of cardiac hypertrophy remains unclear. This study investigated the early changes in serum metabolomic in a pressure overload cardiac hypertrophy model induced by transverse aortic constriction (TAC). Methods The 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 the surgery, cardiac echocardiography was performed to assess cardiac remodeling and function. HE and Masson staining were used to observe the pathologic changes. The plasma metabolites were detected by UPLC-QTOFMS and Q-TOFMS. The specific metabolites of the model were screened by orthogonal partial least squares discriminant analysis (OPLS-DA). The metabolic pathways were characterized by KEGG analysis, and the predictive value of the screened metabolites was analyzed by receiver operating characteristic (ROC) curve analysis. Results Three weeks after the surgery, the TAC and sham groups had similar left heart function and thickness of the interventricular septum and diastolic left ventricular posterior wall. However, in pathologic examination, the cross-sectional area of cardiac myocytes and the severity of myocardial fibrosis were significantly elevated in TAC rats. OPLS-DA analysis showed different metabolic patterns between TAC and sham groups. Based on the criterion of VIP > 1 and p