Premium
Viral delivery of vascular endothelial growth factor (VEGF) rescues angiogenic imbalance in the BPH/5 mouse model of pre‐eclampsia (PE)
Author(s) -
Butler Scott D,
Woods Ashley K,
Hoffmann Darren S,
Sharma Ram V,
Davisson Robin L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.625.12
Subject(s) - angiogenesis , vascular endothelial growth factor , medicine , endocrinology , placental growth factor , andrology , vegf receptors
Pregnant BPH/5 mice exhibit an angiogenic imbalance profile that mirrors women at high risk of developing PE, including diminished levels of circulating VEGF. Serum from pregnant BPH/5 mice (e12.5) shows markedly reduced angiogenic potential in an in vitro angiogenesis assay compared to serum from C57 controls (BPH/5 0.8±0.1 vs. C57 1.3±0.04, normalized to FBS, n= 4‐5, p<.05). Here we hypothesized that by increasing circulating levels of VEGF, we could rescue the angiogenic imbalance in this model. At e7.5, pregnant BPH/5 and C57 were injected via tail vein with an adenovirus encoding VEGF121 or LacZ. VEGF levels were verified using ELISA. A functional angiogenic assay was performed to assess the effect of serum from these mice on tube formation using HUVEC cultures. As expected, serum from LacZ‐treated BPH/5 pregnant mice (e12.5) induced significantly less tube formation than C57 (BPH/5 LacZ 0.9±.01 vs. C57 LacZ 1.3± 0.1, normalized to FBS, p<.05). Importantly, serum from Ad‐VEGF‐treated BPH/5 restored the angiogenic potential to the same levels as C57 (1.3±0.1 normalized to FBS, P<0.05 vs. BPH/5Lacz). Interestingly, Ad‐VEGF therapy had no effect on the angiogenic potential of serum from pregnant C57 mice, indicating an optimal level of circulating angiogenic factors in normal pregnancy. These results highlight the potential for VEGF therapy in high risk pregnancies complicated with angiogenic deficits.