Ecto-5′-nucleotidase (Nt5e/CD73) gene knockout exacerbates vascular remodeling and inflammatory response in mice after intravenous transplantation

doi:10.3969/j.issn.1006-7795.2025.03.016

Abstract

Abstract: Objective To examine the phenotypic characteristics of Ecto-5′-nucleotidase (Nt5e/CD73) gene knockout mice in restenosis of blood vessels after vein transplantation so as to identify potential targets for early diagnosis and drug treatment of vascular restenosis after clinical coronary artery bypass surgery. Methods CD73 gene knockout mice aged 8-10 weeks were used as the experimental group, and the littermate wild-type mice were used as the control group. Using the inferior vena cava of mice as a donor, we transplanted to the right carotid artery of allogeneic mice with a trocar method to establish a mouse inferior vena cava carotid artery vascular transplantation model. At the 4th week post-model establishment, we systematically evaluated the patency of the transplanted blood vessels, the formation of the vascular intima, the proliferation of the media, the morphology of the elastin layer, and the expression of inflammatory factors. The vascular smooth muscle cells (VSMCs) from the inferior vena cava of mice were isolated in vitro, and the migration and proliferation were assessed with CD73 inhibitor adenosine 5'-(alpha, beta-methylene) diphosphate (APCP). Results In CD73 knockout mice, neointima formation was impaired, the elastic fiber layer was disrupted and lost, and medial smooth muscle cells proliferated more actively. These changes ultimately led to decreased vascular wall elasticity and increased blood flow resistance. The immunohistochemical staining results suggest that in CD73 gene knockout mice the transplanted vein tissue showed extensive infiltration of Mac-2 positive macrophages, and the expression of cytokines interleukin-1 β (IL-1 β), IL-6, and transforming growth factor β (TGF-β) was significantly increased. CD73 deficiency exacerbated inflammatory responses and vascular remodeling in venous tissues. Scratch wound healing and cell proliferation assays revealed that CD73 inhibition promoted VSMCs proliferation, yet concurrently impaired their migratory capacity. Conclusion Knockout of the CD73 gene exacerbates vascular remodeling and inflammatory response in vein grafts, offering crucial insights for the precise diagnosis and targeted treatment of patients with CD73 gene defects undergoing coronary artery bypass surgery in clinical practice.

Key words: Nt5e gene, vein graft, vascular restenosis, vascular remodeling, smooth muscle cell

CLC Number:

R654.3

Liu Tingting, Shi Hongtao, Xu Hui, Du jie, Piao Chunmei. Ecto-5′-nucleotidase (Nt5e/CD73) gene knockout exacerbates vascular remodeling and inflammatory response in mice after intravenous transplantation[J]. Journal of Capital Medical University, 2025, 46(3): 511-519.

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