title: Accelerated reendothelialization, increased neovascularization and erythrocyte extravasation after arterial injury in BAMBI-/- mice.
abstract: BACKGROUND
  Intimal injury rapidly activates TGFβ and enhances vascular repair by the growth of endothelial (EC) and vascular smooth muscle cells (VSMC). The response to the TGFβ family of growth factors can be modified by BAMBI (BMP, Activin, Membrane Bound Inhibitor) acting as a non-signaling, competitive antagonist of TGFβ type I receptors such as ALK 1 and 5. In vivo the effect of BAMBI will depend on its cell-specific expression and of that of the ALK type receptors. We recently reported EC restricted BAMBI expression and genetic elimination of BAMBI resulting in an in vitro and in vivo phenotype characterized by endothelial activation and proliferation involving alternative pathway activation by TGFβ through ALK 1.
  
  
  RESULTS
  To test the hypothesis that BAMBI modulates arterial response to injury via its effects on endothelial repair and arterial wall neovascularization we used a model of femoral arterial denudation injury in wild type (WT) and BAMBI(-/-) mice. Arterial response was evaluated at 2 and 4 weeks after luminal endothelial denudation of femoral arteries. The BAMBI(-/-) genotype mice showed accelerated luminal endothelial repair at 2 weeks and a highly unusual increase in arterial wall neovascularization compared to WT mice. The exuberant intimal and medial neovessel formation with BAMBI(-/-) genotype was also associated with significant red blood cell extravasation. The bleeding into the neointima at 2 weeks transiently increased it's area in the BAMBI(-/-)genotype despite the faster luminal endothelial repair in this group. Vascular smooth muscle cells were decreased at 2 weeks in BAMBI(-/-) mice, but comparable to wild type at 4 weeks.
  
  
  CONCLUSIONS
  The absence of BAMBI results in a highly unusual surge in arterial wall neovascularization that surprisingly mimiks features of intra-plaque hemorrhage of advanced atheroma in a mechanical injury model. This suggests important effects of BAMBI on arterial EC homeostasis that need to be further studied in a model of inflammatory atherosclerosis.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guillot
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Kollins
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badimon
authors.forename: Detlef
authors.initials: D
authors.lastname: Schlondorff
authors.forename: Randolph
authors.initials: R
authors.lastname: Hutter
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004912:Erythrocytes / Q000473:pathology*; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism; D006470:Hemorrhage / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D015398:Signal Transduction; D017539:Tunica Intima / Q000293:injuries* / Q000378:metabolism; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing
chemical_list: C485672:Bambi protein, mouse; D008565:Membrane Proteins