Zheng Yang, Ye Cong, Li Haitao, Wang Yudai, Teng Lifeng, Huang Yubing
Department of Cardiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Haikou, 570311, Hainnan, China.
Cardiovasc Toxicol. 2025 May;25(5):735-749. doi: 10.1007/s12012-025-09974-6. Epub 2025 Mar 13.
Heart failure (HF) is a clinical syndrome resulting from cardiac overload and injury. The molecular mechanisms underlying ischemic HF remain unclear. Using the GSE116250 and GSE203160 datasets, we screened for differentially expressed genes (DEGs) in ischemic HF, identifying 132 overlapping genes. Through the protein-protein interaction (PPI) network, we screened nine hub genes-SPP1, POSTN, CCN2, FGF7, OGN, BMP2, LUM, TGFB2, and BMP7-that may serve as diagnostic biomarkers for HF. FGF7 and BMP7 expression levels were reduced, while TGFB2, OGN, and CCN2 expression levels were elevated in rat models of left anterior descending coronary artery ligation. Notably, Cell Counting Kit-8 and flow cytometry showed that TGFB2 knockdown promoted viability and inhibited apoptosis in oxygen glucose deprivation-induced H9c2 cells. Western blot analysis further demonstrated that TGFB2 knockdown decreased cleaved Caspase-3/Caspase-3 and Bax protein levels while increasing Bcl-2 protein expression. These findings reveal that TGFB2 knockdown mitigates ischemic HF by suppressing apoptosis, offering novel insights into the fundamental molecular mechanisms underlying HF.
心力衰竭(HF)是一种由心脏负荷过重和损伤引起的临床综合征。缺血性HF的潜在分子机制尚不清楚。利用GSE116250和GSE203160数据集,我们筛选了缺血性HF中差异表达基因(DEG),鉴定出132个重叠基因。通过蛋白质-蛋白质相互作用(PPI)网络,我们筛选出9个核心基因——SPP1、POSTN、CCN2、FGF7、OGN、BMP2、LUM、TGFB2和BMP7——它们可能作为HF的诊断生物标志物。在左冠状动脉前降支结扎大鼠模型中,FGF7和BMP7表达水平降低,而TGFB2、OGN和CCN2表达水平升高。值得注意的是,细胞计数试剂盒-8和流式细胞术显示,TGFB2基因敲低可促进氧糖剥夺诱导的H9c2细胞的活力并抑制其凋亡。蛋白质印迹分析进一步表明,TGFB2基因敲低可降低裂解的Caspase-3/Caspase-3和Bax蛋白水平,同时增加Bcl-2蛋白表达。这些发现表明,TGFB2基因敲低通过抑制凋亡减轻缺血性HF,为HF潜在的基本分子机制提供了新的见解。