Mitochondrial origins of preeclampsia

Active Project Grant Awarded Last action

Award ID
F32HD123271
Recipient
Awarding agency
Obligated
$79,278

Award facts

Assistance listing
93.865 Child Health and Human Development Extramural Research
Completion date 0% complete
Place of performance
Aurora, CO 80045, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Preeclampsia (PE) is a complex, multisystem vascular disorder of placental origin, affecting 8.5 million pregnancies worldwide each year. PE and its frequent complication, fetal growth restriction (FGR), pose acute threats to maternal and fetal survival and raise the lifetime risk of cardiovascular disease in affected women by two to tenfold. No effective prevention strategies exist, largely due to a limited understanding of the mechanisms underlying their etiology. Evidence points to placental mitochondrial dysfunction as a central driver. In PE, chronic placental ischemia-reperfusion driven by impaired vasodilation of the uteroplacental arteries disrupts mitochondrial function and architecture, impairing cellular energy production and increasing mitochondrial reactive oxygen species (mtros) production. Knowledge gaps remain regarding how mitochondrial network architecture and oxidative capacity regulate vascular function, and whether these represent therapeutic targets. Our goal is to determine how placental mitochondrial network architecture and oxidative capacity interact to regulate uteroplacental vascular function in PE and ultimately FGR. In a high-altitude (HA) cohort, where PE incidence is 3-fold greater than at lower altitudes, we found lower placental mitochondrial oxidative metabolism (oxphos) in PE VS. Controls, with pilot studies implicating defective fatty acid oxidation (FAO) as the primary driver. We hypothesize that placental hypoxia blunts FAO, promoting mitochondrial network fragmentation and elevated mtros, which in turn increase uteroplacental-fetoplacental vascular resistance and precipitate PE. Aim 1 quantifies placental FAO-linked oxphos and mtros production using high-resolution assays. Aim 2 defines mitochondrial network disruptions using machine-learning 3D imaging of mitochondrial morphology and single- nuclei RNA sequencing. Aim 3 integrates metabolic and morphological data with uteroplacental vascular function measures to test whether FAO deficits and mtros serve as mechanistic links between placental hypoxia and impaired vascular function, and whether mitochondrial-targeted antioxidants can restore vascular function. This project will provide the first integrated molecular-to-vascular analysis of placental mitochondrial dysfunction in PE. Expected outcomes include identifying FAO impairment as a core metabolic deficit, delineating mitochondrial network signatures that distinguish PE, and proof-of-concept for mitochondrial-targeted therapies. This project directly advances my long-term goal of building a translational research program investigating how mitochondrial physiology drives hypoxia-related cardiovascular and pregnancy disorders. This proposal will provide structured training in clinical and human research, complementing my background in mitochondrial physiology and animal models. By integrating new molecular and analytical approaches, i will gain critical skills to address maternal and fetal vascular health, preparing me to lead innovative, translational investigations.

Quick answers

Who received award F32HD123271?

F32HD123271 was awarded to The Regents Of The University Of Colorado by National Institute of Child Health and Human Development (National Institutes of Health) on February 1, 2027.

How much is award F32HD123271 worth?

$79,278 has been obligated on F32HD123271.

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