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- W2899247508 abstract "Objectives: Adventitial vasa vasorum provides oxygen and nourishment to the vascular wall, but whether it regulates vascular disease remains unclear. This study aims to determine whether adventitial fibroblast-derived VEGF regulates the formation of vasa vasorum contributing to neointima formation through macrophage recruitment. Methods: Balloon injury procedure was performed in male 12-week-old Sprague-Dawley rats. Wire injury procedure was performed in male 12-week-old c57bl/6 mice. Multiphoton laser scanning microscopy was used for detecting macrophage movement. Results: Vasa vasorum formation was enhanced particularly in the adventitia of injured arteries in a time-dependent manner accompanied by cell proliferation and VEGF expression. Both endogenous and PKH26-labelled exogenous macrophages were mainly distributed in the adventitia around vasa vasorum. Interestingly, perivascular delivery of Ranibizumab preferentially concentrated in the adventitia resulted in a decrease of neointima formation with concurrent reduction of vasa vasorum count and macrophage infiltration. In Tie2-cre/Rosa-LoxP-RFP mice, macrophage rolling, adhesion and transmigration was observed in adventitial vasa vasorum and accelerated neointima formation. In primary cultured adventitial fibroblasts, exogenous VEGF increased VEGF expression and secretion in a time and dose-dependent manner. AF-conditioned medium promoted endothelial cell angiogenesis, vascular cell adhesion molecule-1 expression and macrophage adhesion was blocked by VEGF-neutralizing antibody and VEGFR2 inhibitor ZM323881, which also inhibited activation of VEGFR2/ERK1/2 pathway. Conclusion: These results demonstrate that adventitial fibroblast-derived VEGF plays a significant role in the vasa vasorum formation which promotes macrophage recruitment and neointima formation." @default.
- W2899247508 created "2018-11-09" @default.
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- W2899247508 date "2018-10-01" @default.
- W2899247508 modified "2023-09-25" @default.
- W2899247508 title "A7900 Adventitial Fibroblast-derived VEGF Promotes Vasa Vasorum-associated Neointima Formation by Macrophage Recruitment" @default.
- W2899247508 doi "https://doi.org/10.1097/01.hjh.0000548146.24748.e6" @default.
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