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. 2026 Jan 22;76(2):109391.
doi: 10.1016/j.identj.2025.109391. Online ahead of print.

Serum and Salivary microRNA Biomarkers Reveal Oxidative Stress Dysregulation in Coronary Artery Disease

Anandhi Sekar Arthisri  1 , Vishnu Priya Veeraraghavan  2 , A Thirumal Raj  3 , Raghavendra M Shetty  4 , Shankargouda Patil  5
Affiliations

Serum and Salivary microRNA Biomarkers Reveal Oxidative Stress Dysregulation in Coronary Artery Disease

Anandhi Sekar Arthisri et al. Int Dent J. .

Abstract

Introduction and aim: Coronary artery disease (CAD) is a major cause of death. Epicardial adipose tissue (ECAT) contributes to CAD via oxidative stress, regulated by non-coding RNAs like miRNAs and lncRNAs.

Methods: Oxidative stress-related genes were retrieved from GeneCards. Microarray datasets (GSE64554 and GSE64563) identified differentially expressed genes and miRNAs in ECAT. PPI network and clustering revealed 51 key genes. Bottleneck analysis highlighted CD44, RUNX3, and KLRD1. miR-127-3p, regulating these genes, showed downregulation in ECAT, saliva, and plasma samples from 30 CAD patients.

Results: Out of 407 overlapping oxidative stress genes, 51 were strongly regulated via miRNA-lncRNA networks. CD44, RUNX3, and KLRD1 were key biomarkers. miR-127-3p showed significant downregulation (P < .05) and the highest lncRNA interaction count. Its consistent decrease in ECAT, saliva, and plasma indicates systemic dysregulation in CAD.

Conclusions: CD44, RUNX3, and KLRD1 are oxidative stress biomarkers in ECAT, regulated by miR-127-3p. Its consistent downregulation in ECAT, plasma, and saliva supports its role in CAD pathogenesis and systemic relevance.

Clinical relevance: The consistent downregulation of miR-127-3p in plasma and saliva highlights its potential as a clinically relevant, non-invasive biomarker, supporting early detection and monitoring strategies for CAD through accessible body fluids.

Keywords: Coronary artery disease; Epicardial adipose tissue; Oxidative stress; Plasma; Saliva; miRNAs.

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Conflict of interest statement

Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

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Fig. 1
Overview of the study workflow, including analysis of EAT transcriptomic datasets, identification of miR-127-3p–associated oxidative-stress genes through differential expression and ceRNA analyses, and clinical validation of circulating miR-127-3p by qRT-PCR in saliva and plasma.
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Fig. 2
(A) Differentially expressed genes obtained from the GSE64554 dataset between CAD and control from epicardial adipose tissue. (B) Differentially expressed miRNAs in the GSE64563 dataset between CAD and control from epicardial adipose tissue.
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Fig. 3
Intersection of oxidative stress genes and upregulated CAD genes.
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Fig. 4
Primary protein interaction network employing oxidative stress genes and upregulated genes in ECAT-specific CAD.
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Fig. 5
Top three clusters of oxidative stress-associated CAD genes. (A) Cluster 1, (B) Cluster 2, and (C) Cluster 3.
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Fig. 6
Functional enrichment analysis. (A) Cellular components, (B) biological process, (C) molecular function, and (D) molecular pathways.
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Fig. 7
Common genes between the top three clusters (A) and predicted miRNA target genes (B).
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Fig. 8
The decreased expression of hsa-miR-127-3p in saliva and plasma samples from CAD patients relative to healthy controls.
See this image and copyright information in PMC

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