# Mechanisms of Vascular Toxicity from Inhaled Toxicants

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2022 · $324,648

## Abstract

Air pollution exposure has a well-appreciated negative impact on vascular health. Over the past decade,
several epidemiological reports have highlighted associations between particulate matter (PM) and ozone (O3)
exposures and pregnancy-related events, including preeclampsia, peripartum cardiomyopathy, and adverse
birth outcomes. In the past funding cycle, we have greatly expanded our understanding of the crucial
pathways that are essential to systemic vascular responses to inhaled toxicants. Both particulate matter (PM)
and gaseous pollutants have the capacity to induce proteolytic activity in the lung, leading to the shedding of
protein fragments that are bioactive and promote endothelial inflammatory, antiangiogenic, and
vasoconstrictive responses. We propose to use this knowledge to study the cardiovascular impacts of inhaled
pollutants on maternal physiology during and after pregnancy, periods of vulnerability due to dynamic
metabolic demands, cardiovascular remodeling, and angiogenesis. Our discoveries of vasoactive, endogenous
protein fragments arising from exposure to inhaled pollutants raises questions for how such mechanisms may
impact the highly dynamic cardiovascular system during and after pregnancy. We hypothesize that specific
peptide motifs, shed from the lung in response to air pollutant exposure, can drive uterine arterial constriction
and reduce placental angiogenesis during pregnancy, promoting the pathological feedback mechanisms that
further predispose dams to cardiomyopathic remodeling postpartum. We propose to first characterize the
impact that pulmonary peptidase-derived circulating factors arising from inhaled pollutants exert on uterine
artery and placental endothelial function. We anticipate that peptide fragments shed from the lung after
exposure to ozone O3 or ambient PM can negatively impact uterine artery tone during pregnancy and also
impair placental vasculogenesis, leading to pathological placental insufficiency. Further, we will assess the role
of pulmonary proteinases in creating the serum bioactive components by pharmacological inhibition of matrix
metalloproteinase activity. Second, we will assess how early gestational exposure to pollutants (O3, PM) can
perturb hemodynamic and cardiac structural changes in normal and perturbed models of pregnancy. We posit
that pollutant-induced generation of constrictive factors, along with the placental antiangiogenic response, will
increase uterine artery resistance and maternal systemic arterial blood pressure. Third, we will examine the
pollutant-induced perturbation of normal cardiac hypertrophy pathways during pregnancy and involution
pathways postpartum. We hypothesize that pollutant exposure during pregnancy will promote maladaptive
hypertrophy through suppression of stat3 signaling and also impair cardiac atrophy postpartum, which will lead
to irreversible, functional deficits. Lastly, we will investigate proteomic changes in the amniotic fluid relative to
O3 conc...

## Key facts

- **NIH application ID:** 10457331
- **Project number:** 5R01ES014639-15
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Matthew J Campen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $324,648
- **Award type:** 5
- **Project period:** 2008-05-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457331

## Citation

> US National Institutes of Health, RePORTER application 10457331, Mechanisms of Vascular Toxicity from Inhaled Toxicants (5R01ES014639-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10457331. Licensed CC0.

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