Abstract
STIMULATION OF EPH-B4 PREVENTS ADULT VENOUS REMOLDING IN ARTERIAL ENVIRONMENT

*Roshan Gurung, Guo Yuanyuan, Jin Hui and Nirmal Prasad Sah

ABSTRACT

Introduction: One third of the vein graft failure is due to unsuccessful adaptation characterized by excessive vein wall thickening and loss of venous identity. There is no proper solution till date. Recent studies suggest that Eph-B4, which is determinant of veins during embryonic period and thought to be passive in adulthood, might be responsible for retaining venous identity in adult. As such, we developed rat model vein graft implantation to discover whether stimulation of Eph-B4 prevents vein wall thickening and preserves venous identity in arterial environment. Materials and Method: Suprahepatic inferior vena cava was transplanted from a donor rat into the infrarenal abdominal aorta of a recipient rat. 24 rats were divided into two groups, 12 in Control group and 12 in Intervention group. Half of the vein grafts from each group were harvested after 1 week and the remaining half of the vein grafts were harvested after 4 weeks. Eph-B4 was stimulated by Ephrin-B2/Fc. H&E, immunohistochemical and immunofluorescence staining were performed to study the changes at cellular and molecular level. All the data were analyzed and statistically compared with the help of SPSS 12.0 software. P<0.05 was considered statistically significant. Results: After Ephrin-B2/Fc treatment, vein grafts showed reduced wall thickness and reduced ɑ-actin expression compared with control group vein grafts in 4 weeks. However, no significant difference in wall thickness and ɑ-actin expression was noted in 1 week. Moreover, control group vein grafts showed diminished Eph-B4 expression and loss of venous identity in the arterial environment whereas vein grafts derived from Ephrin-B2/Fc–injected rat showed retention of Eph-B4 expression. Conclusion: Eph-B4 is not only active in adult veins, but it also plays a key role in retention of venous identity by limiting vein wall thickening. Therefore, it is possible to prevent vein graft failure due to unsuccessful adaptation by stimulating Eph-B4. The ability of Ephrin-B2/Fc to stimulate Eph-B4 confined to the vein wall provides new therapeutic strategy.

Keywords: Eph-B4; neointimal hyperplasia; vein graft adaptation; vein graft stenosis.


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