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. 2019 May 9;39(7):1402–1418. doi: 10.1161/ATVBAHA.118.312190

Figure 5.

Figure 5.

HIF (hypoxia-induced factor)-1-VEGF (vascular endothelial growth factor)-A-VEGFR2 signaling is required for hypoxia-induced pathological choriocapillary (CC) remodeling in zebrafish. A, Analysis of Vegfr1, Vegfr2a (kdrl), or Vegfr2b (kdr) mRNA expression in CCs from normoxia (N) or hypoxia (H) exposed adult fli1a:EGFP zebrafish, normalized to the expression of Fli1a. n=26. ***P<0.001. B, Quantitative PCR analysis of Vegfaa, Vegfab, Plgf (placental growth factor), or Vegfb mRNA expression in CCs from normoxia (N) or hypoxia (H) exposed adult fli1a:EGFP zebrafish, normalized to the expression of Gapdh. n=16–24. **P<0.01. C, Confocal micrographs of CCs from adult fli1a:EGFP zebrafish exposed normoxia or hypoxia and treated with DMH4, alternatively from adult hypoxia-exposed fli1a:EGFP zebrafish (Wt), fli1a:EGFP;hif1aa−/−;hif1ab−/− zebrafish (HIF1a−/−), or fli1a:EGFP;Hsp70:VEGFAA-DN zebrafish incubated for 1 h at 37°C daily from day 4 of hypoxia treatment (Vegfaa-DN). White arrowheads point to hypoxia-induced extravascular columns in the CCs. Size bars indicate 25 µm. D, Quantification of the number of extravascular columns in the CCs from the experiment shown in C. N=normoxia, H=hypoxia, Hi=fli1a:EGFP;hif1aa−/−;hif1ab−/− zebrafish, V=fli1a:EGFP;Hsp70:VEGFAA-DN zebrafish, D=DMH4-treatment zebrafish. n=10–15. ANOVA P<0.0053, Tukey post hoc: *P<0.05. NS indicates not significant.