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NIH grant 1K01HL188214-01: Maternal midlife vascular pathophysiology following pregnancy: impact of placental health and function
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: Andrea Corrie Kozai. Award: $141178.
Start: 2026-09-05T00:00:00.
Preeclampsia, a hypertensive disorder of pregnancy, is associated with a higher risk of long-term maternal
cardiovascular disease. Placental dysfunction is a hallmark of preeclampsia and is hypothesized as a
mechanism linking preeclampsia with later disease. Maternal vascular malperfusion lesions, which represent
placental dysfunction that impacts clinical presentation of preeclampsia, can be identified following delivery
through histology of placenta tissue. Further, preeclampsia presents with features of maternal systemic vascular
reactivity and understanding how these features persist into midlife will inform intervention targets. However, few
studies exist linking measures of placental dysfunction to future maternal vascular reactivity. This project will
leverage the Window Brain study, an existing prospective cohort study spanning pregnancy through 15 years
following delivery. The Window Brain study is following women in whom preeclampsia status was recorded and
placental evaluation determined the presence or absence of maternal vascular malperfusion lesions and
examining associations with brain health. The proposed project will pilot test a novel continuous quantification of
vascularization in the placenta through immunohistochemistry of stored placenta specimens, which will amplify
the characterization of placental small vessel disease in the Window Brain cohort. Then, we will determine how
features of placental health are associated with vascular reactivity 15-20 years after delivery in these participants.
Specifically, we will test how 1) preeclampsia status with or without maternal vascular malperfusion lesions and
2) placental villous vascularization as measured by our novel immunohistochemistry method are associated with:
a) vascular response to a functional exercise stress test; b) microvascular reactivity and perfusion; and c) arterial
stiffness. Finally, we will 3) evaluate cross-sectional associations between our vascular health measures and
circulating biomarkers of vascular reactivity to identify potential therapeutic targets. The training goals included
in this proposal will support the research aims and prepare the candidate to pursue a larger independent study
utilizing resting and functional measures of vascular health and multiple indices of placental structure and
function. This training will incorporate knowledge and skills development in 1) exercise physiology assessment
techniques; 2) vascular biology assessment and analysis; and 3) advanced placenta analytic techniques related
to preeclampsia and long-term maternal cardiometabolic sequelae. These training goals will extend and enhance
the candidate’s current strength in women’s health and cardiovascular epidemiology. By providing the skills and
knowledge to launch an independent program of research using metrics of vascular reactivity, this training plan
will allow the candidate to elucidate the impact of placental small vessel disease on long-term disease
development. These research and training goals will inform future vascular assessments in a well-powered
ancillary to an existing cohort or intervention trial by identifying pathophysiological targets.document fetched 2026-09-10 22:51