title: Metallothionein enhances angiogenesis and arteriogenesis by modulating smooth muscle cell and macrophage function.
abstract: OBJECTIVE
  In a previous study we identified metallothionein (MT) as a candidate gene potentially influencing collaterogenesis. In this investigation, we determined the effect of MT on collaterogenesis and examined the mechanisms contributing to the effects we found.
  
  
  RESULTS
  Collateral blood flow recovery was assessed using laser Doppler perfusion imaging, and angiogenesis was measured using a Matrigel plug assay. Smooth muscle cells were isolated from MT knockout (KO) mice for functional assays. Gene expression of matrix metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth factor, and Fat cadherin in smooth muscle cells was measured by real-time polymerase chain reaction, and protein levels of vascular endothelial growth factor and matrix metalloproteinase-9 were determined using enzyme-linked immunosorbent assay and Western blot. CD11b(+) macrophages were tested for invasiveness using a real-time impedance assay. Both flow recovery and angiogenesis were impaired in MT KO mice. Proliferation, migration, and invasion were decreased in MT KO smooth muscle cells, and matrix metalloproteinase-9, platelet-derived growth factor, and vascular endothelial growth factor expression were also decreased, whereas FAT-1 cadherin expression was elevated. MT KO CD11b(+) cells were more invasive than wild-type cells.
  
  
  CONCLUSIONS
  MT plays an important role in collateral flow recovery and angiogenesis, an activity that appears to be mediated, in part, by the effects of MT on the functionality of 3 cell types essential for these processes: endothelial cells, smooth muscle cells, and macrophages.
authors.affiliation: Cardiovascular Research Institute, MedStar Research Institute, 108 Irving Street, NW, Room 214, Washington, DC 20010, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Zbinden
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wang
authors.forename: Remi
authors.initials: R
authors.lastname: Adenika
authors.forename: Marcel
authors.initials: M
authors.lastname: Schmidt
authors.forename: Justin U
authors.initials: JU
authors.lastname: Tilan
authors.forename: Amir H
authors.initials: AH
authors.lastname: Najafi
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Peng
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Lassance-Soares
authors.forename: Micaela
authors.initials: M
authors.lastname: Iantorno
authors.forename: Hakim
authors.initials: H
authors.lastname: Morsli
authors.forename: Leonid
authors.initials: L
authors.lastname: Gercenshtein
authors.forename: Gil Jin
authors.initials: GJ
authors.lastname: Jang
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
authors.forename: Mary Susan
authors.initials: MS
authors.lastname: Burnett
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology / Q000254:growth & development*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology
chemical_list: D008668:Metallothionein