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. 2017 Apr;55:49-54.
doi: 10.1016/j.leukres.2017.01.017. Epub 2017 Jan 10.

Simvastatin Ameliorates Graft-Vs-Host Disease by Regulating angiopoietin-1 and angiopoietin-2 in a Murine Model

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Simvastatin Ameliorates Graft-Vs-Host Disease by Regulating angiopoietin-1 and angiopoietin-2 in a Murine Model

Peng Zheng et al. Leuk Res. .

Abstract

Angiopoietins play an important role in vascular endothelial function. Endothelial damage is an important pathogenesis relating with acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), protecting endothelial cells (ECs) from damage may be a potent prophylaxis and therapeutic strategy of acute GVHD (aGVHD). In this study, we explored changes in Angiopoietin-1 (Ang-1) and Ang-2 expression in a aGVHD mouse model and determined whether simvastatin prevents GVHD through regulating Ang-1 and Ang-2 expression. In vitro simvastatin administration increased Ang-1 production and release but conversely inhibited Ang-2 release from EA.hy926 ECs. Simvastatin improved the survival of aGVHD mice, attenuated the histopathological GVHD grades and plasma levels of Ang-2, and elevated the plasma levels of Ang-1 as well as the aortic endothelial levels of Ang-1 and Ang-2. In summary, simvastatin represents a novel approach to combat GVHD by increasing Ang-1 production while suppressing Ang-2 release to stabilize endothelial cells.

Keywords: Angiopoietin; Endothelial damage; Graft-versus-host disease; Simvastatin.

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