title: Simvastatin ameliorates graft-vs-host disease by regulating angiopoietin-1 and angiopoietin-2 in a murine model.
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.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qiu-Ling
authors.initials: QL
authors.lastname: Wu
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Li
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Di-Min
authors.initials: DM
authors.lastname: Nie
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ling-Hui
authors.initials: LH
authors.lastname: Xia
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Collaborative Center of Hematology, Soochow University, Suzhou, China. Electronic address: meihongcncn@aliyun.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
mesh_terms: D042683:Angiopoietin-1 / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D042702:Angiopoietin-2 / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D000818:Animals; D001011:Aorta / Q000166:cytology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D051379:Mice; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D019821:Simvastatin
keywords: Angiopoietin; Endothelial damage; Graft-versus-host disease; Simvastatin