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Knockdown of TGFB2 Attenuates Ischemic Heart Failure by Inhibiting Apoptosis
Yang Zheng1, Cong Ye1, Haitao Li1
1Department of Cardiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Haikou, 570311, Hainnan, China.
Insights
Researchers identified key genes in ischemic heart failure (HF). TGFB2 knockdown reduced apoptosis and improved cell viability, offering new therapeutic insights for HF.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Genomics
Background:
- Heart failure (HF) is a complex clinical syndrome often caused by cardiac overload and injury.
- The precise molecular mechanisms driving ischemic heart failure (HF) are not fully understood.
- Identifying novel molecular targets is crucial for developing effective HF treatments.
Purpose of the Study:
- To identify key molecular players and potential diagnostic biomarkers in ischemic heart failure (HF).
- To elucidate the role of specific genes, particularly TGFB2, in the pathogenesis of ischemic HF.
- To investigate the therapeutic potential of targeting TGFB2 in mitigating HF progression.
Main Methods:
- Differential gene expression analysis of ischemic HF datasets (GSE116250, GSE203160) to identify overlapping differentially expressed genes (DEGs).
- Construction and analysis of a protein-protein interaction (PPI) network to identify hub genes.
- Validation of gene expression changes in a rat model of myocardial infarction (left anterior descending coronary artery ligation).
- In vitro experiments using H9c2 cells subjected to oxygen-glucose deprivation (OGD) to assess the effects of TGFB2 knockdown on cell viability and apoptosis (Cell Counting Kit-8, flow cytometry, Western blot).
Main Results:
- 132 overlapping DEGs were identified between the two HF datasets.
- Nine hub genes (SPP1, POSTN, CCN2, FGF7, OGN, BMP2, LUM, TGFB2, BMP7) were identified as potential diagnostic biomarkers for HF.
- In rat models, FGF7 and BMP7 expression decreased, while TGFB2, OGN, and CCN2 expression increased.
- TGFB2 knockdown in OGD-induced H9c2 cells significantly enhanced cell viability and suppressed apoptosis.
- TGFB2 knockdown led to decreased cleaved Caspase-3/Caspase-3 and Bax, and increased Bcl-2 protein levels, indicating reduced apoptosis.
Conclusions:
- TGFB2 plays a critical role in the apoptosis pathway associated with ischemic heart failure (HF).
- Knockdown of TGFB2 demonstrates a protective effect by inhibiting apoptosis and promoting cell survival in an in vitro model of ischemic injury.
- Targeting TGFB2 presents a promising therapeutic strategy for mitigating ischemic HF progression.
Abstract:
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.
