Coronary Artery Disease Variant rs7173743 Modulates miR-184–Dependent Extracellular Matrix Pathways in Human Vascular Tissue

Clin Res Cardiol (2026). DOI 10.1007/s00392-026-02870-1
A. Sawant (Rīga)¹, M. Schwab (München)², G. Lepsaya (Rīga)¹, K. D. Neiburga-Vigante (Rīga)¹, F. Starnecker (München)², J. Krefting (München)³, C. Hehshaus (München)⁴, C. Friess (München)⁴, I. Pugach (München)⁴, D. Breucker (München)⁴, K. Wenger (München)⁴, S. Mahajan (München)⁴, Z. Chen (München)⁵, T. Keßler (München)², F. Voll (München)², S. Cassese (München)⁶, H. Sager (München)⁶, T. Trenkwalder (München)², E. Xhepa (München)², L. Li (München)⁴, C. Yang (München)⁴, M. Mokry (Utrecht)⁷, G. Pasterkamp (Utrecht)⁸, M. U. Kaikkonen-Määttä (Kuopio)⁹, D. Bongiovanni (Augsburg)¹⁰, L. Maegdefessel (München)¹¹, S. Doppler (München)¹², H. Lahm (München)⁶, M. Dreßen (München)¹², M. Krane (München)⁶, H. Schunkert (München)², B. Vilne (München)², M. von Scheidt (München)^2
1Bioinformatics Group, Rīga Stradiņš University Rīga, Lettland; ²Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; ³Deutsches Herzzentrum München Klink für Herzkreislauferkrankungen München, Deutschland; ⁴Deutsches Herzzentrum München, TUM Universitätsklinikum München, Deutschland; ⁵TUM Klinikum Rechts der Isar Klinik und Poliklinik für Innere Medizin I München, Deutschland; ⁶Deutsches Herzzentrum München München, Deutschland; ⁷Central Diagnostics Laboratory, University Medical Center Utrecht Utrecht, Niederlande; ⁸University Medical Center Utrecht Department of Experimental Cardiology Utrecht, Niederlande; ⁹A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland Kuopio, Finnland; ¹⁰Universitätsklinikum Augsburg I. Medizinische Klinik Augsburg, Deutschland; ¹¹TUM Klinikum Rechts der Isar Klinik für Vaskuläre und Endovaskuläre Chirurgie München, Deutschland; ¹²Deutsches Herzzentrum München Klinik für Herz- und Gefäßchirurgie München, Deutschland

Aim: Most coronary artery disease (CAD)–associated variants are located in noncoding regions, but their functional impact in vascular tissue remains unclear. This study investigated whether the CAD-risk variant rs7173743 modulates the expression of microRNA-184 (miR-184) and its downstream extracellular matrix (ECM)–related pathways in human arteries.

Methods: Internal mammary artery (IMA) samples from 192 patients in the Personalized Risk Prediction in Coronary Artery Disease 2 (PRECAD2) cohort were analyzed by integrating genome-wide genotype and miRNA sequencing data. miRNA expression quantitative trait locus (miR-eQTL) mapping was performed using adjusted linear models with false discovery rate (FDR) correction. Results were validated using the STARNET and GTEx datasets. Predicted and validated miR-184 targets were subjected to correlation and pathway enrichment analyses.

Results: The CAD-risk allele (T) of rs7173743 was associated with higher miR-184 expression in vascular tissue (β = 0.15, P = 8.0×10⁻³, FDR < 0.05). Directionally consistent associations for ADAMTS7 and CTSH were observed in STARNET and GTEx arteries. Among 134 expressed miR-184 targets, significant enrichment was identified for ECM organization, transforming growth factor-β signaling, and vascular remodeling pathways, including ELN, LTBP1, and NOX4. Correlation analyses revealed inverse relationships between miR-184 and these targets, suggesting an rs7173743–miR-184–ECM regulatory axis in the vascular wall.

Conclusions: This study identifies rs7173743 as a vascular miR-eQTL for miR-184, linking noncoding genetic variation to ECM-related gene networks in human arteries. These findings provide a mechanistic link between genetic variation and vascular gene regulation, offering new targets for studying CAD pathogenesis.