# Novel role for placental endothelial mitochondria in preeclampsia

> **NIH NIH K08** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $150,870

## Abstract

Project Summary
This K08 application is for Dr. Jennifer McIntosh, an assistant professor of Maternal Fetal Medicine at the Medical
College of Wisconsin who is building her research niche as a physician-scientist studying mitochondrial
dysfunction within the human placenta as a mechanism for preeclampsia. This award would afford Dr. McIntosh
the time and resources that she needs to develop the research project and collaborative relationships. She has
established mentoring and consultative teams that include Dr. David Gutterman, an expert in human vascular
reactivity in the microcirculation, Dr. Hartmut Weiler, an expert in cellular and molecular mechanisms relating to
coagulation and placental development, Dr. Allen Cowley, an integrative physiologist internationally recognized
for his research in hypertension, and Dr. Nicole Lohr, an expert in vascular biology and experience with the
placental vasculature. Dr. McIntosh has also woven in experience with outside institutions to gain expertise in
cutting edge placental techniques as well as mitochondrial next generation sequencing to ensure she achieves
her career development goals and research aims. Preeclampsia remains a worldwide problem with over 10
million pregnant women impacted and over half a million perinatal lives lost annually. Preeclampsia is on the
rise, and the underlying pathophysiological mechanism of preeclampsia remains poorly understood. Vascular
dysfunction and endothelial damage within the placenta and maternal vasculature contribute to hypertensive
disorders of pregnancy. A novel relationship may exist between mitochondrial damage and endothelial
dysfunction and subsequent development of preeclampsia. The overall hypothesis is that with decreased
placental perfusion, ischemia results in increased reactive oxygen species, inflammation, and release of
mitochondrial DNA damage (mtDNA) that, via TLRs, promote a pro-oxidative and inflammatory environment in
the placental vasculature that result in endothelial dysfunction that culminates in preeclampsia. To investigate
this hypothesis, Dr. McIntosh will 1) determine whether placental hypoxia induces mtDNA damage using
placental samples within a hypoxic environment and 2) test whether heightened mtDNA damage in vessels from
preeclamptic placentas is responsible for impaired endothelial dependent dilation via toll-like receptors.
Videomicroscopy and wire myography will be used to test vasodilator capacity, flow mediated dilation (FMD),
and altered FMD as a result of heightened mtDNA in vessels from placentas in those with preeclampsia and
whether that could be reversed by inhibiting toll-like receptors. These studies may provide a mechanism that can
ultimately be targeted for therapeutic intervention. Through Dr. McIntosh’s proposed career development plan,
she will become an expert in the vascular biology of the human placental microcirculation and mitochondrial
dysfunction. These skills will position Dr. McIntosh to develop her R01 ...

## Key facts

- **NIH application ID:** 10308479
- **Project number:** 5K08HL150340-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Jennifer J McIntosh
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $150,870
- **Award type:** 5
- **Project period:** 2019-12-17 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308479

## Citation

> US National Institutes of Health, RePORTER application 10308479, Novel role for placental endothelial mitochondria in preeclampsia (5K08HL150340-03). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10308479. Licensed CC0.

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