Vein Graft Failure: Pathophysiology, Detection, Prevention and Emerging Therapeutic Strategies

Abstract Coronary (CABG) and peripheral artery bypass graft (PABG) surgery remain cornerstones of cardiac and vascular surgery respectively. They utilise the saphenous vein as the preferred conduit, although it suffers from poor mid- and long-term outcomes, with the grafted vein often becoming occluded. Current therapeutic approaches aim to manage complications rather than prevent graft failure directly, and despite progress, failure rates have remained unchanged in decades, meaning there remains an unmet clinical need for novel therapeutic approaches. As access to the grafted tissue is available at the time of surgery, CABG and PABG are particularly suited to perioperative therapeutic manipulation and intervention which can be delivered locally and directly to the tissue immediately prior to grafting. Ongoing research attempts to uncover novel genes driving bypass graft failure that can be targeted for such therapies. In addition to protein-coding genes, multiple examples of non-coding genes driving graft failure are now described, including microRNAs and long non-coding RNAs with cell type-specific roles. The increasing wealth of single cell, single nuclei and spatial transcriptomic data related to cardiovascular pathologies are revealing novel target loci which could facilitate greater specificity for target manipulation in specific pathogenic cell types. In parallel, extensive research continues to develop advanced imaging techniques which can be used to monitor the patency of grafts over time, and guide the effective design of advanced therapies. Here, we discuss the progress in these areas and highlight how harmony amongst these will accelerate therapeutic progress towards vein graft disease.