title: Distinct Differences on Neointima Formation in Immunodeficient and Humanized Mice after Carotid or Femoral Arterial Injury.
abstract: Percutaneous coronary intervention is widely adopted to treat patients with coronary artery disease. However, restenosis remains an unsolved clinical problem after vascular interventions. The role of the systemic and local immune response in the development of restenosis is not fully understood. Hence, the aim of the current study was to investigate the role of the human immune system on subsequent neointima formation elicited by vascular injury in a humanized mouse model. Immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl(NSG) mice were reconstituted with human (h)PBMCs immediately after both carotid wire and femoral cuff injury were induced in order to identify how differences in the severity of injury influenced endothelial regeneration, neointima formation, and homing of human inflammatory and progenitor cells. In contrast to non-reconstituted mice, hPBMC reconstitution reduced neointima formation after femoral cuff injury whereas hPBMCs promoted neointima formation after carotid wire injury 4 weeks after induction of injury. Neointimal endothelium and smooth muscle cells in the injured arteries were of mouse origin. Our results indicate that the immune system may differentially respond to arterial injury depending on the severity of injury, which may also be influenced by the intrinsic properties of the arteries themselves, resulting in either minimal or aggravated neointima formation.
authors.affiliation: Department of Pathology and Medical Biology-Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jill
authors.initials: J
authors.lastname: Moser
authors.affiliation: Department of Pathology and Medical Biology-Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Joris
authors.initials: J
authors.lastname: van Ark
authors.affiliation: Department of Pathology, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Marcory C
authors.initials: MC
authors.lastname: van Dijk
authors.affiliation: Diabetes Center of Excellence, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.affiliation: Department of Pathology and Medical Biology-Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.affiliation: Department of Pathology and Medical Biology-Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jan-Luuk
authors.initials: JL
authors.lastname: Hillebrands
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000276:immunology* / Q000469:parasitology / Q000628:therapy; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000276:immunology* / Q000293:injuries / Q000637:transplantation; D006083:Graft Occlusion, Vascular / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D016513:Mice, SCID / Q000276:immunology / Q000293:injuries; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000473:pathology; D058426:Neointima / Q000276:immunology / Q000503:physiopathology; D057772:Vascular System Injuries / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy