title: Endoglin has a crucial role in blood cell-mediated vascular repair.
abstract: BACKGROUND
  Endoglin, an accessory receptor for transforming growth factor-beta in vascular endothelial cells, is essential for angiogenesis during mouse development. Mutations in the human gene cause hereditary hemorrhagic telangiectasia type 1 (HHT1), a disease characterized by vascular malformations that increase with age. Although haploinsufficiency is the underlying cause of the disease, HHT1 individuals show great heterogeneity in age of onset, clinical manifestations, and severity.
  
  
  RESULTS
  In situ hybridization and immunohistochemical analysis of mouse and human hearts revealed that endoglin is upregulated in neoangiogenic vessels formed after myocardial infarction. Microvascularity within the infarct zone was strikingly lower in mice with reduced levels of endoglin (Eng+/-) compared with wild-type mice, which resulted in a greater deterioration in cardiac function as measured by magnetic resonance imaging. This did not appear to be because of defects in host inflammatory cell numbers in the infarct zone, which accumulated to a similar extent in wild-type and heterozygous mice. However, defects in vessel formation and heart function in Eng+/- mice were rescued by injection of mononuclear cells from healthy human donors but not by mononuclear cells from HHT1 patients.
  
  
  CONCLUSIONS
  These results establish defective vascular repair as a significant component of the origin of HHT1. Because vascular damage or inflammation occurs randomly, it may also explain disease heterogeneity. More generally, the efficiency of vascular repair may vary between individuals because of intrinsic differences in their mononuclear cells.
authors.affiliation: Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
authors.forename: Linda W
authors.initials: LW
authors.lastname: van Laake
authors.forename: Sander
authors.initials: S
authors.lastname: van den Driesche
authors.forename: Simone
authors.initials: S
authors.lastname: Post
authors.forename: Alie
authors.initials: A
authors.lastname: Feijen
authors.forename: Maurits A
authors.initials: MA
authors.lastname: Jansen
authors.forename: Mariette H
authors.initials: MH
authors.lastname: Driessens
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Mager
authors.forename: Repke J
authors.initials: RJ
authors.lastname: Snijder
authors.forename: Cornelius J J
authors.initials: CJ
authors.lastname: Westermann
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Cees J A
authors.initials: CJ
authors.lastname: van Echteld
authors.forename: Peter
authors.initials: P
authors.lastname: ten Dijke
authors.forename: Helen M
authors.initials: HM
authors.lastname: Arthur
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.forename: Franck
authors.initials: F
authors.lastname: Lebrin
authors.forename: Christine L
authors.initials: CL
authors.lastname: Mummery
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003331:Coronary Vessels; D000071063:Endoglin; D006579:Heterozygote; D006801:Humans; D008026:Ligation; D051379:Mice; D009000:Monocytes / Q000637:transplantation*; D009154:Mutation; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics; D020257:Ventricular Remodeling; D014945:Wound Healing
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface