Integrated Systems Biology Identifies Disruptions in Mitochondrial Function and Metabolism as Key Contributors to HFpEF

HFpEF accounts for ∼50% of HF cases. The ZSF1-obese rat model recapitulates clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and diastolic dysfunction. Here, we used a systems biology approach to define the metabolic and transcriptional signatures to gain mechanistic insight into pathways contributing to HFpEF development. The integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential interventional target.射血分数保留型心力衰竭（Heart Failure with Preserved Ejection Fraction, HFpEF）约占心力衰竭（Heart Failure, HF）病例总数的50%。ZSF1肥胖大鼠模型（ZSF1-obese rat model）可重现射血分数保留型心力衰竭的临床特征，包括高血压、肥胖、代谢综合征、运动耐量减退与舒张功能障碍。本研究采用系统生物学（systems biology）方法解析代谢与转录组特征，以深入阐明参与射血分数保留型心力衰竭发生发展的信号通路机制。本研究应用的整合多组学（integrated omics）策略可为揭示射血分数保留型心力衰竭潜在的新型基因、代谢物及信号通路提供研究框架，其中重点将线粒体能量代谢（mitochondrial energy metabolism）作为潜在干预靶点。