Pregnancy is a powerful and complex stressor for women. Our central theme is that provoked placental and maternal microvascular responses to pregnancy cause overlapping adverse peripartum events in subsets of women and more generally herald trajectories toward future cardiovascular disease (CVD). Project 1 tests the hypothesis that placental vascular pathology provides an untapped lens through which we can view and define early vascular pathology that marks women at high risk of CVD. Here we aim to show that placental markers herald maternal microvascular dysfunction in the decade after the pregnancy.
Project 2 evaluates the glycocalyx (GC), a protective coating on vascular endothelial cells, as a mechanism of microvascular dysfunction and downstream CVD. We propose that women evidencing both maternal GC failure during pregnancy and placental pathology will be especially prone to GC failure and microvascular dysfunction 1 year post pregnancy, and that this will be most evident in preeclampsia consistent with especially high risk of future CVD.
Project 3 uses mouse models to ask complimentary questions not otherwise addressable, 1) Do pregnancy and pregnancy-specific hypertension affect the development of future CVD?, and 2) Does the nutraceutical L-citrulline beneficially affect placentation, the GC, microvascular function, and attenuate atherosclerotic progression? Our projects synergistically elucidate how pregnancy informs about CVD mechanisms and trajectories in the years after delivery. We have developed an integrated women’s health training program for an obstetrical fellow, a cardiology or internal medicine fellow, and a basic science trainee. Our focus on pregnancy-evoked vascular phenomena informing later life CVD complements other Go Red Centers.
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