Safeguarding VSMC Contractile Phenotype With In Situ circRNA-mediated Endothelial Olaratumab Engineering to Prevent Vascular Graft Stenosis - PubMed
9 hours ago
- #circRNA translation
- #vascular grafts
- #VSMC phenotype
- Small-diameter vascular grafts (SDVGs) often fail due to restenosis caused by endothelial cell (EC)-derived PDGF-BB, which shifts vascular smooth muscle cells (VSMCs) to a synthetic phenotype.
- A circRNA-based in situ antibody engineering strategy was developed to functionalize SDVGs, reprogramming ECs to secrete Olaratumab (Ola), a PDGFR-α-neutralizing antibody, to modulate EC-VSMC signaling.
- In vitro, Ola engineering reversed PDGF-BB-induced VSMC phenotypic switching, suppressing migration, invasion, and excessive extracellular matrix deposition by attenuating MAPK and PI3K-AKT pathways.
- In rat models, this approach enabled sustained local antibody secretion for up to 24 days, accelerated endothelialization, and reduced neointimal hyperplasia and graft calcification over 6 months.
- CircRNA-based in situ antibody engineering offers a powerful way to modulate intercellular crosstalk and sustain the VSMC contractile phenotype, lowering the risk of SDVG restenosis.