INTRODUCTION: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide. Identifying reliable biomarkers for early diagnosis and understanding the underlying molecular mechanisms are critical for improving patient outcomes. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers due to their stability in blood and involvement in various pathophysiological processes. This pilot case-control study aims to perform small RNA sequencing using next-generation sequencing in the plasma of Indian CAD patients to identify differentially expressed miRNAs and evaluate their potential as biomarkers. METHODS: Plasma samples were collected from 30 angiographically verified CAD patients and 30 age-and gender-matched controls with normal coronary arteries. Small RNA libraries were prepared and sequenced using Illumina's NextSeq 2000. Differentially expressed miRNAs were identified using the DESeq2 package, followed by target gene prediction using the miRDB, TargetScan, and miRTarBase databases. Functional enrichment analysis was performed using DAVID. RESULTS: Twelve significantly dysregulated circulating miRNAs were identified in CAD patients. miR-6806-3p, miR-3614-5p, miR-548e-3p, miR-147b-3p, and let-7d-3p demonstrated novel associations with CAD, whereas miR-125a-3p, miR-495-3p, and miR-143-3p were highlighted for their significant roles in regulating key molecular pathways implicated in CAD pathogenesis. DISCUSSION: This study represents the first comprehensive NGS-based analysis of small RNAs in the plasma of Indian CAD patients. The twelve identified circulating miRNAs highlight their intricate roles in CAD pathogenesis by targeting key target genes involved in critical biological pathways. CONCLUSION: The identified miRNAs highlight their potential as diagnostic biomarkers; however, validation in larger and more diverse cohorts is required to confirm their clinical utility.
Mestry et al. (2026) studied this question.