Grant: Travel Awards - Institute Community Support

BACKGROUND: Preeclampsia is a disorder of pregnancy linked to later maternal cardiovascular disease. However, cardiovascular health in children from these pregnancies is less studied. Placental growth factor (PGF) promotes blood vessel growth and is low in the blood of preeclamptic women. Fetal PGF concentration may also be low since PGF expression is found before blastocyst development. Blood pressure measurement using radiotelemetry in mice lacking PGF (Pgf-/-) identified stroke after blockage of one carotid artery. In normal mice, brain blood flow is maintained through other carotid artery via the circle of Willis. We hypothesized that lack of PGF impaired developmental vascularization of the brain, predisposing the mice to stroke. METHODS: Blood vessels in the brains of male and female Pgf-/- mice were compared to Pgf+/+ mice. The developing hindbrain, retina and circle of Willis as well as the adult retinal vascular bed were investigated using Isolectin B4, a marker of endothelial cells. The adult carotid arteries and circle of Willis were imaged and quantified using ink perfusion. RESULTS: Hindbrain vascularization was delayed in Pgf-/- fetuses but recovered before birth. Pgf-/- retinal vascular development was also impaired, particularly in adult males. Pregnant Pgf-/- mice also had deviations in their retinal vasculature. The circle of Willis differed in Pgf-/- female mice with fewer connecting arteries present. There was no statistically significant difference in carotid artery diameter or abnormality. CONCLUSIONS: Overall, PGF has a role in cerebral vascular development of the central nervous system that displays sexual dimorphism. Lack of PGF altered the retinal vasculature in males and the circle of Willis in females. Changes to the circle of Willis may explain the increased stroke risk in Pgf-/- mice. These results have implications for the cerebrovascular and neurodevelopmental health of children born to preeclamptic mothers.