Parallel culprit-thrombus transcriptomic and genome-wide association analyses in ST-segment elevation myocardial infarction: An exploratory pilot study.

BACKGROUND

Direct molecular characterization of culprit coronary thrombi may provide insights into local mechanisms of ST-segment elevation myocardial infarction (STEMI) that are not captured by circulating blood. We investigated thrombus-associated transcriptomic patterns and their relationship with inherited genetic susceptibility.

METHODS

High-depth RNA sequencing was performed on paired aspirated culprit thrombi and peripheral blood from 10 patients with first-time STEMI. Differential expression was assessed using DESeq2, with exploratory signals defined by nominal P < 0.05 and absolute log2 fold change ≥ 1.5. Benjamini-Hochberg correction was applied across 44,525 transcripts. Transcript-clinical associations and sensitivity analyses were also performed. In parallel, a genome-wide association study included 1787 patients with STEMI and 17,837 age- and sex-matched controls.

RESULTS

Although 708 transcripts met the nominal exploratory criteria, none remained significant after transcriptome-wide correction. The nominal signals converged on biologically relevant processes, including extracellular matrix remodeling, inflammatory and chemokine signaling, lipid and apolipoprotein regulation, angiogenesis, and metalloprotease activity. These patterns likely reflected both local thrombus biology and differences in cellular composition between thrombi and peripheral blood. Clinical correlations and differences according to prior coronary artery disease were not robust after multiplicity correction or sensitivity analysis. Genome-wide association analysis identified rs74755602 at the MASTL locus (odds ratio, 2.08; 95% confidence interval, 1.65-2.63; P = 7.85 × 10-10), but MASTL showed no corresponding differential expression.

CONCLUSION

Paired thrombus-blood profiling revealed coherent but exploratory transcriptomic patterns related to thrombosis, inflammation, and vascular remodeling. The independent MASTL association lacked transcriptomic concordance, supporting cautious interpretation and further functional validation.