TY - JOUR
T1 - Metallothionein enhances angiogenesis and arteriogenesis by modulating smooth muscle cell and macrophage function
AU - Zbinden, Stephan
AU - Wang, Jinsong
AU - Adenika, Remi
AU - Schmidt, Marcel
AU - Tilan, Justin U.
AU - Najafi, Amir H.
AU - Peng, Xinzhi
AU - Lassance-Soares, Roberta M.
AU - Iantorno, Micaela
AU - Morsli, Hakim
AU - Gercenshtein, Leonid
AU - Jang, Gil Jin
AU - Epstein, Stephen E.
AU - Burnett, Mary Susan
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Endothelial cell
KW - Macrophage
KW - Neovascularization
KW - Smooth muscle cell
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U2 - 10.1161/ATVBAHA.109.200949
DO - 10.1161/ATVBAHA.109.200949
M3 - Article
C2 - 20056912
AN - SCOPUS:77649110581
VL - 30
SP - 477
EP - 482
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 3
ER -