Methotrexate Therapy Promotes Cell Coverage and Stability in in-Stent Neointima

Area of Science:

• Cardiovascular Research
• Pharmacology
• Biomedical Engineering

Background:

• Drug-eluting stents (DES) utilize anti-proliferative drugs that can impede vascular healing and increase late stent thrombosis risk.
• Optimizing DES therapy requires balancing anti-proliferative effects with pro-healing mechanisms to ensure stent patency and patient safety.

Purpose of the Study:

• To investigate the effects of systemic methotrexate (MTX) on vascular healing, cell coverage, and inflammation following stent implantation.
• To elucidate the in vitro molecular mechanisms by which MTX influences endothelial cell behavior and inflammatory responses.

Main Methods:

• A rabbit common carotid artery stenting model was used to assess MTX's impact on cell coverage and inflammation via serial optical coherence tomography (OCT).
• In vitro studies utilized human umbilical vein endothelial cells (HUVECs) to explore MTX's effects on apoptosis, proliferation, and inflammatory signaling pathways.

Main Results:

• Low-dose MTX significantly improved cell coverage and vascular healing, evidenced by reduced uncovered stent struts at 4 weeks.
• MTX treatment led to more stable neointima at 12 weeks, with decreased heterogeneity, microvessels, and low-signal-intensity layers.
• In vitro, MTX inhibited HUVEC apoptosis, enhanced proliferation, and suppressed inflammatory activation via the PI3K/AKT pathway.

Conclusions:

• Low-dose systemic MTX promotes early cell coverage and vascular healing after stenting by modulating inflammatory responses.
• MTX contributes to neointimal stability post-stenting, potentially by targeting inflammatory pathways.
• MTX represents a promising therapeutic strategy to improve stent outcomes by enhancing healing and reducing thrombotic risk.