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Time-dependent pathobiological and physiological changes of implanted vein grafts in a canine model

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Abstract

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.

Graphical abstract

The implanted vein graft within the arterial environment undergoes pathobiological processes through RhoA and YAP activity, leading to pathophysiological changes.

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Abbreviations

NI:

Neo-intimal

PAOD:

Peripheral arterial occlusive disease

CAOD:

Coronary artery obstructive disease

VSMC:

Vascular smooth muscle cell

PCNA:

Proliferation cell nuclear antigen

IL-1β :

Interleukin-1β

RhoA:

Ras homolog gene family, member A TNF-α tumor necrosis factor- α

SMC:

Smooth muscle cell

YAP:

Yes-associated protein

CFD:

Computational fluid dynamics

WSS:

Wall shear stress

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Acknowledgements

The authors acknowledge the veterinary staff that provided anesthesia support during the procedure.

Funding

This research was supported by a grant of the Korea Health Technology R&D project through 342 the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health 343 & Welfare, Republic of Korea (grant number: HI18C1237), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A1A01060374).

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Authors and Affiliations

  1. 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

    Eui Hwa Jang, Jung-Hwan Kim, Ji-yeon Ryu, Hyo-Hyun Kim & Young-Nam Youn

  2. Department of Mechanical Engineering, YONSEI University, Seoul, 03722, South Korea

    Jiyong Lee

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Correspondence to Young-Nam Youn.

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Jang, E.H., Kim, JH., Ryu, Jy. et al. Time-dependent pathobiological and physiological changes of implanted vein grafts in a canine model. J. of Cardiovasc. Trans. Res. 15, 1108–1118 (2022). https://doi.org/10.1007/s12265-022-10226-z

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