Molecular profiling of coronary stent restenosis: A systematic review and functional analysis of implicated genes

Clinical Snapshot

Key Findings

• P Value: Not reported for individual gene associations; pathway enrichment p-values from Enrichr/ClueGO not specified in available data

• Effect Size: Not reported; no pooled quantitative effect size calculated. Findings are descriptive: multiple genes implicated in extracellular matrix remodelling, inflammatory signalling, and the renin-angiotensin system

• Primary Outcome: Identification of genes and biological pathways associated with DES-related coronary restenosis across 17 included studies

• Nnt Or Sensitivity: Not applicable; no clinical outcome data synthesised. Bioinformatic enrichment analysis confirmed overrepresentation of ECM remodelling, inflammatory, and RAS pathways — specific enrichment statistics not reported in abstract

• Confidence Interval: Not reported

Clinical Application

Direct clinical application is not currently feasible. Genetic testing for restenosis risk prediction is not standard of care. The identified pathways (ECM remodelling, RAS, inflammation) are biologically plausible targets but require validation in prospective cohort studies and randomised trials before clinical translation. Bioinformatic tools used (Enrichr, Cytoscape/ClueGO) are freely available for research use In Australia, DES implantation is the dominant PCI strategy, with second-generation DES (e.g., everolimus-eluting, zotarolimus-eluting stents) listed on the Prostheses List (AIHW). Restenosis rates with contemporary DES are approximately 5-10%, representing a clinically significant burden given Australia's high PCI volume (approximately 55,000 procedures annually per AIHW data). The RACGP and Cardiac Society of Australia and New Zealand (CSANZ) do not currently recommend routine genetic testing for restenosis risk. The RAS pathway findings are of particular relevance given the widespread use of ACE inhibitors and ARBs (PBS-listed) in Australian post-PCI patients, though no direct pharmacogenomic recommendations can be drawn from this review. TGA has not approved any pharmacogenomic test for restenosis risk stratification. This review may inform future Australian research priorities in interventional cardiology genomics. Adult patients undergoing PCI with DES implantation, particularly those at elevated risk of in-stent restenosis. Findings are most relevant to research contexts and hypothesis generation for future pharmacogenomic or precision cardiology studies rather than immediate clinical application

Abstract

BACKGROUND: Coronary stent restenosis occurs in approximately 5% of patients treated with drug-eluting stents (DES) and is associated with adverse clinical outcomes. Elucidating the genetic mechanisms underlying restenosis may support precision medicine approaches to improve patient management.This systematic review aimed to synthesize evidence on genes and biological pathways associated with DES-related restenosis and to perform functional analysis of the implicated genes using bioinformatics tools. METHODS: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. A systematic search of PubMed, Scopus, and Web of Science was performed for human studies investigating genetic or genomic factors in coronary restenosis, with the last search conducted in March 2024. Eligibility criteria included original studies reporting genetic associations with DES restenosis. Screening and data extraction were performed by a single reviewer. Identified genes underwent gene set enrichment analysis using Enrichr (Ma'ayan Laboratory, Computational Systems Biology) and ClueGo extension on Cytoscape (National Resource for Network Biology). RESULTS: Seventeen studies met the inclusion criteria. The studies highlighted multiple genes involved in extracellular matrix remodeling, inflammatory signaling, and the renin-angiotensin system. Gene enrichment analysis confirmed the overrepresentation of these biological pathways in DES-associated restenosis. CONCLUSIONS: This systematic review synthesizes the genetic and molecular contributors to DES-associated restenosis and identifies potential targets for future research and personalized therapies. No external funding was received, and the protocol was not registered.

References

1. 1.El Mansouri, R., Habbal, R., & Dehbi, H. (2026). Molecular profiling of coronary stent restenosis: A systematic review and functional analysis of implicated genes. Genetics and Molecular Research. https://doi.org/10.4238/gmr18641