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). 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 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. Three 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. Disruption 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.

中文翻译：

---

赖氨酸降解异常与压力超负荷大鼠早期心肌细胞肥大的发展有关


心肌细胞代谢在心脏重塑之前发生变化，但其在早期心脏肥大检测中的作用仍不清楚。本研究调查了主动脉横缩（TAC）诱导的压力超负荷心脏肥大模型中血浆代谢组学的早期变化。 TAC模型是通过部分结扎主动脉弓构建的。 12 只 Sprague-Dawley 大鼠被随机分为 TAC 组（n = 6）和假手术组（n = 6）。手术后三周，进行心脏超声心动图以评估心脏重塑和功能。采用苏木精/伊红（HE）、Masson、麦芽凝集素（WGA）染色观察病理变化。通过UPLC-QTOFMS和Q-TOFMS检测血浆代谢物。通过正交偏最小二乘判别分析（OPLS-DA）筛选特定代谢物。通过京都基因和基因组百科全书（KEGG）分析对代谢途径进行表征，并通过受试者工作特征（ROC）曲线分析来分析筛选代谢物的预测价值。术后三周，TAC 组和假手术组的左心功能、室间隔和舒张期左心室后壁厚度相似。然而，病理检查发现TAC大鼠心肌细胞横截面积和心肌纤维化严重程度显着升高。 OPLS-DA 显示 TAC 组和假手术组之间不同的代谢模式。根据VIP > 1且P < 0.05的标准，筛选出13种代谢物。 KEGG 分析发现相关代谢物 5-氨基戊酸、N6-乙酰基-L-赖氨酸和 L-赖氨酸导致赖氨酸降解受到破坏，ROC 曲线下面积 (AUC) 分别为 0.917、0.889 和 0。806，分别用于预测代偿性心肌细胞肥大。赖氨酸降解的破坏可能与早期心脏肥大的发展有关，相关代谢物可能是亚临床心肌细胞肥大的潜在预测和干预靶标。