Time-dependent pathobiological and physiological changes of implanted vein grafts in a canine model
Eui Hwa Jang1, Jung-Hwan Kim1, Ji-Yeon Ryu1
1Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 250 Seongsanro, Seodaemun-gu, Seoul, 03722, South Korea.
Journal of Cardiovascular Translational Research
|March 4, 2022
Summary
Understanding vein graft failure is crucial for effective treatments. This study reveals how pathobiological processes, involving RhoA and YAP activity, drive vein graft remodeling and failure in arterial environments.
Area of Science:
- Vascular Biology
- Biomedical Engineering
- Surgical Research
Background:
- Autologous vein grafting is a critical surgical procedure.
- High rates of vein graft failure necessitate further investigation into underlying mechanisms.
- Current clinical interventions for vein graft failure lack clarity, highlighting the need for novel therapeutic strategies.
Purpose of the Study:
- To analyze the complex relationship between pathobiological and physiological processes in preclinical vein graft models.
- To elucidate the molecular mechanisms driving vascular remodeling and failure in implanted vein grafts.
- To identify potential therapeutic targets for improving vein graft patency and long-term outcomes.
Main Methods:
- A canine model was utilized to study interposition femoral vein grafts.
- Measurements included graft expansion, velocity, neointima (NI) formation, and NI/Media ratio over time (8 and 12 weeks).
- Analysis of mechanical properties, RhoA-mediated tumor necrosis factor-alpha (TNF-α) induction, and YAP activity was performed.
Main Results:
- Graft expansion and velocity peaked at 8 weeks, decreasing by 12 weeks post-implantation.
- Neointima formation and the NI/Media ratio increased significantly over time, indicating progressive vascular remodeling.
- RhoA-mediated TNF-α was induced by rapid structural changes and high shear stress; YAP activity influenced SMC proliferation, differentiation, apoptosis, and autophagy.
Conclusions:
- Vein grafts implanted in an arterial environment undergo significant pathobiological changes.
- Time-dependent physiological alterations, driven by RhoA and YAP activity, contribute to vein graft remodeling and eventual failure.
- Understanding these pathobiological processes offers a potential strategy for developing treatments to prevent vein graft failure.
