Extended Data Fig. 6: VEGF mRNA LNP 55 reduces liver enzyme levels in serum and improves placental blood vessel area in hypoxia-induced pre-eclampsia.
From: Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia
Hypoxia-induced pre-eclampsia was established through i.v. administration of 1 × 109 plaque forming units (PFU) of soluble Fms-like tyrosine kinase-1 adenovirus (Adv-sFlt-1) on gestational day E7.5. 1 mg kg−1 VEGF mRNA LNPs 55 or 98 were then administered i.v. on gestational day E11. a–d, Maternal weight change was recorded daily (a), and on gestational day E17 (b) total litter weight, (c) litter size, and (d) albumin concentration in urine were measured. e–j, Serum levels of (e) VEGF, (f) alanine transaminase (ALT), (g) aspartate aminotransferase (AST), (h) tumour necrosis factor (TNF), (i) interleukin-6 (IL-6), and (j) interferon-γ (IFNγ) were evaluated on gestational days E11.5 and E17. k, Placental vasculature in the labyrinth was visualized with H&E staining; stained sections were used to quantify mean blood vessel area. l, Similarly, renal histology was visualized using H&E staining with arrows indicating glomeruli. Maternal weight change, total litter weight, litter size, urine albumin concentration, and serum protein levels are reported as the mean ± s.e.m. (Adv-sFlt-1 + VEGF mRNA LNP 55: n = 5 biological replicates; PBS, Adv-sFlt-1: n = 4 biological replicates; Adv-sFlt-1 + VEGF mRNA LNP 98: n = 3 biological replicates). Mean blood vessel area is reported as the median with the 25th and 75th percentiles (1–2 placentas per mouse, 2 sections per placenta, 2–3 images per section). Ordinary (b–d) or nested (k) two-sided, one-way ANOVAs or ordinary two-sided, two-way ANOVAs (a, e–j) with post hoc Student’s t tests using the Holm-Šídák correction for multiple comparisons were used to compare responses across treatment groups.
