Integrated Protein and Gene Expression Analysis of S100A1 and S100A8/A9 Demonstrates Coordinated Dysregulation of Calcium Homeostasis, Innate Immune Activation, and Angiogenic Signaling in Acute Myocardial Infarction

Document Type : Research Paper

Authors

College of Medicine, Babylon University, Hillah, Iraq

10.22103/jab.2026.27154.1897

Abstract

Objective
Acute myocardial infarction (AMI) is characterized by complex molecular interactions involving disruption of cardiomyocyte calcium homeostasis, activation of innate immune pathways and impaired angiogenic signaling. However, the integrated relationship between the cardiomyocyte-specific S100A1 protein and the inflammatory S100 A8/A9 complex remains incompletely understood. Thus, this study aimed to evaluate the protein and gene expression profiles of S100A1 and S100A8/A9 and their association with inflammatory (TNF-α) and angiogenic (VEGF-A) biomarkers in AMI.
Materials and methods
This case-control study included 176 participants (88 AMI patients and 88 age and sex matched controls). Participants were recruited from AL-Hilla Teaching Hospital and Marjan Medical City. Circulating levels of S100A1, S100A8/A9, TNF-α and VEGF-A were measured using ELISA, while serum calcium was quantified with spectrophotometry. Gene expression levels of S100A1, S100A8 and S100A9 were determined by qRT-PCR using 2^−ΔΔCt method. Apply receiver operating characteristic (ROC) curve analysis to assess diagnostic performance.
Results
Significant multi-axis dysregulation was observed in AMI patients. S100A1 mRNA expression was markedly reduced (p<0.0001), accompanied by decreased circulating S100A1 protein (AUC = 0.69Y, specificity = 100%). In contrast, inflammatory markers were elevated with S100A8/A9 demonstrating acceptable diagnostic performance (AUC=0.76), while TNF-α showed no discriminative value (AUC=0.50). Serum calcium exhibited strong diagnostic accuracy (AUC=0.82), indicating early disruption of calcium homeostasis. Angiogenic impairment was reflected by reduced VEGF-A levels but with limited diagnostic utility (AUC = 0.54). Gene expression analysis further confirmed significant upregulation of S100A8 (p=0.030) and S100A9 (p=0.044). No significant correlation was observed between S100A1 and inflammatory markers (p>0.05), whereas S100A8 and S100A9 expression showed a strong positive association, indicating coordinated inflammatory activation.
Conclusion
These findings show that calcium control linked to S100A1, immune responses from S100A8/A9 and issues with blood vessel formation related to VEGF-A are all connected. The superior diagnostic capability of S100A1 suggests that markers reflecting calcium management in cardiac cells may enhance the identification of acute myocardial infarction (AMI) and provide greater insight than conventional inflammatory indicators.

Keywords

References

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Agricultural Biotechnology Journal
Volume 18, Issue 3
June 2026
Pages 477-504

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