title: Preexisting smooth muscle cells contribute to neointimal cell repopulation at an incidence varying widely among individual lesions.
abstract: BACKGROUND
  With the diverse origin of neointimal cells, previous studies have documented differences of neointimal cell lineage composition across models, but the animal-to-animal difference has not attracted much attention, although the cellular heterogeneity may impact neointimal growth and its response to therapeutic interventions.
  
  
  METHODS
  R26R(+);Myh11-CreER(+), and R26R(+);Scl-CreER(+) mice were used to attach LacZ tags to the preexisting smooth muscle cells (SMCs) and endothelial cells (ECs), respectively. Neointimal lesions were created via complete ligation of the common carotid artery (CCA) and transluminal injury to the femoral artery (FA).
  
  
  RESULTS
  LacZ-tagged SMCs were physically relocated from media to neointima and changed to a dedifferentiated phenotype in both CCA and FA lesions. The content of SMCs in the neointimal tissue, however, varied widely among specimens, ranging from 5 to 70% and 0 to 85%, with an average at low levels of 27% and 29% in CCA (n = 15) and FA (n = 15) lesions, respectively. Bone marrow cells, although able to home to the injured arteries, did not differentiate fully into SMCs after either type of injury. Preexisting ECs were located in the subendothelial region and produced mesenchymal marker α-actin, indicating endothelial-mesenchymal transition (EndoMT); however, EC-derived cells represented only 7% and 3% of the total neointimal cell pool of CCA (n = 7) and FA (n = 7) lesions, respectively. ECs located on the luminal surface exhibited little evidence of EndoMT.
  
  
  CONCLUSIONS
  Neointimal hyperplasia proceeds with a wide range of variation in its cellular composition between individual lesions. Relative to ECs, SMCs are major contributors to the lesion-to-lesion heterogeneity in neointimal cell lineage composition.
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, United States.
authors.forename: Pu
authors.initials: P
authors.lastname: Yang
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hong
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, United States.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Fu
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, United States.
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Schmit
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, Georgia, United States.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Su
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, United States; The Malcom Randall VAMC, Gainesville, FL, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Berceli
authors.affiliation: Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, United States. Electronic address: jiangzh@surgery.ufl.edu.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017536:Carotid Artery, Common / Q000503:physiopathology*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology*; D005263:Femoral Artery / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D058426:Neointima / Q000503:physiopathology*