Association of the Serpine1 with the Obesity Paradox in Ischemic Heart Failure

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Zhu Xiaoqiu; Hua Junyan

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Journal Paper

Paper Information

Journal: IRANIAN JOURNAL OF PUBLIC HEALTH Year:2025 | Volume:54 | Issue:7 Page(s): 1516-1529

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Information Journal Paper

Title

Association of the Serpine1 with the Obesity Paradox in Ischemic Heart Failure

Author(s)

Zhu Xiaoqiu | Hua Junyan | Issue Writer Certificate

Keywords

Microarray; Plasminogen activator inhibitor 1; Heart failure; Obesity

Abstract

Background: Extreme obesity pathology is with a risk factor for heart failure (HF), whereas the obesity paradox in HF shows that obese subjects had a good prognosis. The mechanism underlying the obesity paradox in HF prognosis is unclear till now. We aimed to provide evidence for the molecular mechanisms of the obesity paradox in HF.
Methods: Differentially expressed genes (DEGs) in ischemic HF samples were identified in the GSE57338 and GSE5406 datasets. Weighted gene co-expression network analysis (WGCNA) modules and a protein-protein interaction network (PPI) were constructed. HF-associated DEGs and pathways were screened in the Comparative Toxicogenomics Database (CTD). The expression of hub genes in adipose tissues from obese patients and LV samples from HF patients were validated in microarray datasets.
Results: Three HF-associated WGCNA modules were identified and DEGs were associated with the ‘hsa04115: p53 signaling pathway’. SERPINE1 was the only common gene between DEGs and HF-associated genes in the CTD database. The SERPINE1 gene was downregulated in the white adipose tissues compared with brown adipose tissues (P = 3.90e-03) and was upregulated in the omental adipose tissues from obese patients compared with lean subjects (P = 3.85e-02).
Conclusion: The downregulation of SERPINE1 expression might be responsible for the obesity paradox in HF via interacting with ESR1.

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