LAUSR

Vascular dysfunction in women with preeclampsia is complex. Placenta-derived circulating factors and/or the maternal response to these factors contribute to vascular endothelial cell dysfunction. Risk factors for preeclampsia include many conditions such as maternal aging, pre-existing hypertension, obesity and diabetes. The heterogeneity of this population, including the diversity of circulating factors such as oxLDL, TNF α , and advanced glycation end products, has contributed to the overall complexity of targeting a specific pathway for therapeutic prevention and/or intervention. Interestingly, these circulating factors are also among the factors known to upregulate and/or activate the lectin-like oxidized LDL receptor-1 (LOX-1). Our laboratory has shown that LOX-1 is increased in the systemic vasculature of women with preeclampsia and contributes to vascular oxidative stress. Moreover, our rat model of reduced uteroplacental perfusion (RUPP), which has preeclampsia-like signs, demonstrates increased LOX-1 expression, increased vascular oxidative stress and ultimately vascular dysfunction. Since LOX-1 has multiple ligands, it may be a point of convergence for many plasma factors known to be elevated in preeclampsia; including placental-derived microparticles; a current area of investigation. Notably, pregnancy has an important influence on both short- and long-term cardiovascular outcomes for women and their offspring. One risk factor for preeclampsia is maternal age, an important factor considering that the age at which women experience their first pregnancy has steadily increased through the decades. We use aged female rats (9.5 months; equivalent to ∼35 yr old human), to investigate the impact of maternal aging on later-life maternal and offspring cardiovascular health. Our data show that advanced maternal age worsens postpartum vascular function and that offspring born from aged dams have an altered cardiovascular risk profile that is sex-specific. These data further illustrate pregnancy as a window of opportunity to assess both maternal and offspring future cardiovascular risk.