Metallothionein enhances angiogenesis and arteriogenesis by modulating smooth muscle cell and macrophage function

Stephan Zbinden, Jinsong Wang, Remi Adenika, Marcel Schmidt, Justin U. Tilan, Amir H. Najafi, Xinzhi Peng, Roberta M. Lassance-Soares, Micaela Iantorno, Hakim Morsli, Leonid Gercenshtein, Gil Jin Jang, Stephen E. Epstein, Mary Susan Burnett

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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. Methods and 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. Conclusion-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.

Original languageEnglish (US)
Pages (from-to)477-482
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number3
StatePublished - Mar 2010
Externally publishedYes


  • Angiogenesis
  • Endothelial cell
  • Macrophage
  • Neovascularization
  • Smooth muscle cell

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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