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Fig. 3

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ZDB-IMAGE-130326-13
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Figures for Mugoni et al., 2013
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Fig. 3

Block of Mevalonate Pathway Causes Cardiovascular Failure in Zebrafish Embryos by Reducing CoQ10 Synthesis(A) Wild-type (WT) embryos at 72 hpf treated from 54 hpf with statin (mevastatin) or DMSO. Statin treatments induce a bar-like phenotype which is characterized by hemorrhages (asterisk) and heart failure (arrowhead). Scale bar, 300 µm.(B) Three dimensional projections of trunk vessels at 72 hpf of DMSO and statin-treated zebrafish embryos. Statin treatments induce specific endothelial vessels regression and fragmentation in DA and Se (arrows). Scale bar, 100 µm.(C) Quantification of bar-like phenotype after statin treatments. MEV, mevastatin 500 nM; SIM, simvastatin 500 nM; MEN, mevinolin 500 nM.(D) and cholesterol (E) detected by HPLC-UV analyses in statin-treated embryos.(F and G) Bright-field (F) and fluorescent (G) images of Tg(kdrl:GFP)s843ubiad1+/+ and ubiad1+/- embryos at 65 hpf treated with mevastatin (2.5 nM and 5 nM) from 32 to 50 hpf. Treatment with a low dose of statin caused hemorrhages (asterisks) and altered heart morphology (arrowheads) in ubiad1+/-, but not in ubiad1+/+ embryos. Although treatment with a low dose of statin did not induce specific alterations of the main vasculature, ubiad1+/- embryos showed head vasculature, Se, and DA regression; scale bar, 300 µm.(H) Images of Tg(kdrl:GFP)s843ubiad1+/+ and ubiad1+/- embryos trunk vasculature show thinner and collapsed Se and DA morphology in statin-treated ubiad1+/- but not in ubiad1+/+ embryos. Scale bar, 75 µm.(I) Penetrance of bar-like phenotype at 65 hpf after treatment with mevastatin. ubiad1+/- embryos are significantly more sensitive to develop a bar-like phenotype than normal embryos (ubiad1+/+).(J) CoQ10 supplemented embryos show less susceptibility to statin treatments in terms of developing a bar-like phenotype as indicated by histograms showing the percentage of statin-treated embryos having bar-like phenotype after exogenous CoQ10 delivery.(K) CoQ10 supplementation before statin treatment prevents cardiac edema (arrowhead) and brain hemorrhages (asterisk) in barolo. Images of vehicle- and CoQ10-injected embryos after statin treatment. Scale bar, 300 µm.(L) Histograms show oxidative stress in embryos after statin treatment with or without CoQ10.All data are means ± SEM. p < 0.001.See also Figure S3.

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Reprinted from Cell, 152(3), Mugoni, V., Postel, R., Catanzaro, V., De Luca, E., Turco, E., Digilio, G., Silengo, L., Murphy, M.P., Medana, C., Stainier, D.Y., Bakkers, J., and Santoro, M.M., Ubiad1 Is an Antioxidant Enzyme that Regulates eNOS Activity by CoQ10 Synthesis, 504-518, Copyright (2013) with permission from Elsevier. Full text @ Cell