title: Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice.
abstract: OBJECTIVE
  Recent studies of bone marrow (BM)-transplanted apoE knockout (apoE-/-) mice have concluded that a substantial fraction of smooth muscle cells (SMCs) in atherosclerosis arise from circulating progenitor cells of hematopoietic origin. This pathway, however, remains controversial. In the present study, we reexamined the origin of plaque SMCs in apoE-/- mice by a series of BM transplantations and in a novel model of atherosclerosis induced in surgically transferred arterial segments.
  
  
  RESULTS
  We analyzed plaques in lethally irradiated apoE-/- mice reconstituted with sex-mismatched BM cells from eGFP+ apoE-/- mice, which ubiquitously express enhanced green fluorescent protein (eGFP), but did not find a single SMC of donor BM origin among approximately 10,000 SMC profiles analyzed. We then transplanted arterial segments between eGFP+ apoE-/- and apoE-/- mice (isotransplantation except for the eGFP transgene) and induced atherosclerosis focally within the graft by a recently invented collar technique. No eGFP+ SMCs were found in plaques that developed in apoE-/- artery segments grafted into eGFP+ apoE-/- mice. Concordantly, 96% of SMCs were eGFP+ in plaques induced in eGFP+ apoE-/- artery segments grafted into apoE-/- mice.
  
  
  CONCLUSIONS
  These experiments show that SMCs in atherosclerotic plaques are exclusively derived from the local vessel wall in apoE-/- mice.
authors.affiliation: Department of Cardiology, Research Unit, Aarhus University Hospital, Brendstrupgaardsvej, 8200 Aarhus N, Denmark. jben@ki.au.dk
authors.forename: Jacob F
authors.initials: JF
authors.lastname: Bentzon
authors.forename: Charlotte
authors.initials: C
authors.lastname: Weile
authors.forename: Claus S
authors.initials: CS
authors.lastname: Sondergaard
authors.forename: Johnny
authors.initials: J
authors.lastname: Hindkjaer
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.forename: Erling
authors.initials: E
authors.lastname: Falk
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006949:Hyperlipidemias / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins