代谢基因的差异表达区分了生理性和病理性心肌肥大
Differential expression of metabolic genes distinguishes physiological from pathological cardiac hypertrophy.
摘要(中文译文)
心肌肥厚是对生理性或病理性刺激的适应性或非适应性反应，其功能结局各不相同。代谢重编程在这一过程中发挥关键作用；然而，不同重构模式背后的代谢相关基因仍不清楚。从基因表达综合数据库（Gene Expression Omnibus）获取与心肌肥厚相关的转录组芯片数据（GSE776）。通过将生理性（运动诱导）和病理性（高盐饮食诱导）肥厚模型与对照组进行比较，鉴定差异表达基因（DEGs）。从分子特征数据库（MSigDB）中检索代谢相关基因，并与生理性肥厚特异性DEGs取交集，以鉴定候选代谢基因。进行蛋白质-蛋白质相互作用（PPI）分析以鉴定枢纽基因。利用妊娠诱导生理性肥厚和异丙肾上腺素诱导病理性肥厚的小鼠模型、异丙肾上腺素处理的新生大鼠心肌细胞以及人心肌组织样本进行实验验证。转录组分析鉴定出48个与生理性心肌肥厚特异性相关的基因，这些基因主要富集于代谢通路。将这些基因与代谢相关基因集取交集，发现22个与生理性肥厚相关的代谢基因。PPI分析鉴定出HADHA、ACOX1和GOT2为关键枢纽基因。体内和体外实验表明，这些基因在生理性心肌肥厚中显著上调，而在病理性肥厚中显著下调。人心肌组织的免疫组化分析证实，与非肥厚对照相比，病理性肥厚心肌中HADHA、ACOX1和GOT2的表达降低。HADHA、ACOX1和GOT2的差异表达凸显了脂肪酸氧化和线粒体能量代谢的改变是区分生理性和病理性心肌肥厚的关键特征。
Abstract
Cardiac hypertrophy is an adaptive or maladaptive response to physiological or pathological stimuli, with distinct functional outcomes. Metabolic reprogramming plays a key role in this process; however, the metabolism-associated genes underlying different remodeling patterns remain unclear. Transcriptomic microarray data related to cardiac hypertrophy (GSE776) were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by comparing physiological (exercise-induced) and pathological (high-salt diet-induced) hypertrophy models with controls. Metabolism-associated genes were retrieved from the Molecular Signatures Database (MSigDB) and intersected with physiological hypertrophy-specific DEGs to identify candidate metabolic genes. Protein-protein interaction (PPI) analysis was performed to identify hub genes. Experimental validation was performed using mouse models of pregnancy-induced physiological hypertrophy and isoproterenol-induced pathological hypertrophy, isoproterenol-treated neonatal rat cardiomyocytes, and human myocardial tissue samples. Transcriptomic analysis identified 48 genes specifically associated with physiological cardiac hypertrophy, which were predominantly enriched in metabolic pathways. Intersection of these genes with metabolism-related gene sets revealed 22 physiological hypertrophy-related metabolic genes. PPI analysis identified HADHA, ACOX1 and GOT2 as key hub genes. In vivo and in vitro experiments demonstrated that these genes were significantly upregulated in physiological cardiac hypertrophy but markedly downregulated in pathological hypertrophy. Immunohistochemical analysis of human myocardial tissues confirmed reduced expression of HADHA, ACOX1 and GOT2 in pathological hypertrophic myocardium compared with non-hypertrophic controls. Differential expression of HADHA, ACOX1, and GOT2 highlights altered fatty acid oxidation and mitochondrial energy metabolism as key features distinguishing physiological and pathological cardiac hypertrophy.
如何引用
AMA
Xiaojian Cai, Sihuang Lin, Jiangwei Chen, Quanfu Dai, Yong Diao, Liling Zheng. Differential expression of metabolic genes distinguishes physiological from pathological cardiac hypertrophy.. BMC cardiovascular disorders. 2026; doi:10.1186/s12872-026-06129-5.
APA
Xiaojian Cai, Sihuang Lin, Jiangwei Chen, Quanfu Dai, Yong Diao, Liling Zheng (2026). Differential expression of metabolic genes distinguishes physiological from pathological cardiac hypertrophy.. BMC cardiovascular disorders. https://doi.org/10.1186/s12872-026-06129-5
GB/T 7714
Xiaojian Cai, Sihuang Lin, Jiangwei Chen, Quanfu Dai, Yong Diao, Liling Zheng. Differential expression of metabolic genes distinguishes physiological from pathological cardiac hypertrophy.[J]. BMC cardiovascular disorders, 2026 doi:10.1186/s12872-026-06129-5.
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