Grant: Travel Awards - Institute Community Support

Preeclampsia is a hypertensive syndrome that occurs during pregnancy and is the leading cause of maternal disease and death worldwide. Even though the causes of preeclampsia are unknown, this syndrome negatively impacts the function of the mother's (maternal) blood vessels. In preeclampsia, the amount of oxidized-LDL (bad) cholesterol (oxLDL) increases, which binds to its receptor (LOX-1) on the blood vessels, thereby damaging the function of the blood vessels. In this study, we evaluated the mechanisms by which oxLDL can result in a detrimental effect on the maternal blood vessel function during pregnancy. To evaluate our research question, we designed an experimental model of preeclampsia by feeding pregnant mice a diet high in cholesterol (HC) between mid-gestation to the end of pregnancy. The mice on our preeclampsia model (HC-diet) had a lower weight, and the fetuses and placenta weights were also decreased compared to the controls. Moreover, we evaluated the maternal blood vessel function and observed impaired blood vessel function via LOX-1 in the mice on the HC-diet compared to controls. Because the placenta plays a vital role in the development of preeclampsia and can also impact blood vessel function, we evaluated if the placentas were affected by the HC-diet. We found that HC-diet increased the production of harmful molecules in the placenta, which could affect the function of the placenta. Overall, the high cholesterol diet during pregnancy compromised pregnancy outcomes, potentially by negatively affecting the function of the placenta and blood vessels, as seen in preeclampsia. We will continue to investigate the specific mechanisms for this dysfunction in order to identify the vascular mechanisms that could potentially lead to novel therapeutic strategies for preeclampsia.