Division 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.
Department of Mechanical Engineering, YONSEI University, Seoul, 03722, South Korea.
J Cardiovasc Transl Res. 2022 Oct;15(5):1108-1118. doi: 10.1007/s12265-022-10226-z. Epub 2022 Mar 4.
Although autologous vein grafting is essential, the high vein failure rate and specific clinical interventions are not clear, so a potential treatment is critically needed; thus, complex analyses of the relationship between pathobiological and physiological processes in preclinical are essential. The interposition of the femoral vein was performed in a canine model. Maximized expansion and velocity were measured at 8 weeks post-implantation, and a relative decrease was observed at 12 weeks. However, NI formation and NI/Media ratio significantly increased time dependently, and differences between the mechanical properties were observed. Additionally, RhoA-mediated TNF-α induced by rapid structural changes and high shear stress was confirmed. After adaptation to the arterial environment, vascular remodeling occurred by SMC proliferation and differentiation, apoptosis and autophagy were induced through YAP activity without vasodilation and RhoA activity. Our results show that understanding pathobiological processes in which time-dependent physiological changes contribute to vein failure can lead to a potential strategy. The implanted vein graft within the arterial environment undergoes pathobiological processes through RhoA and YAP activity, leading to pathophysiological changes.
虽然自体静脉移植是必不可少的，但静脉高失败率和具体的临床干预措施尚不清楚，因此迫切需要潜在的治疗方法；因此，对临床前病理生物学和生理学过程之间关系进行复杂分析是至关重要的。在犬模型中进行股静脉间置。在植入后 8 周测量最大扩张率和速度，在 12 周时观察到相对减少。然而，NI 形成和 NI/Media 比值随时间显著增加，观察到力学性能的差异。此外，还证实了快速结构变化和高剪切应力诱导的 RhoA 介导的 TNF-α。在适应动脉环境后，通过 SMC 增殖和分化发生血管重塑，通过 YAP 活性诱导细胞凋亡和自噬，而没有血管扩张和 RhoA 活性。我们的结果表明，了解导致静脉衰竭的时间依赖性生理变化的病理生物学过程，可以为潜在的治疗策略提供思路。植入动脉环境内的静脉移植物通过 RhoA 和 YAP 活性经历病理生物学过程，导致病理生理变化。
