# Early Life Stress-induced Reprogramming of Ambulatory Blood Pressure and Vascular Function in Adolescence

> **NIH NIH P01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $335,551

## Abstract

PROJECT 3 SUMMARY
Early life stress (ELS) was strongly linked with adult-onset cardiovascular disease (CVD) over 20 years ago but
remains an under-appreciated CVD risk factor. More than half of U.S. adults report ELS exposures such as
household dysfunction, abuse, or neglect in childhood. Our publications have shown that adults with ELS have
increased indicators for future CVD risk, including casual blood pressure (BP), pulse wave velocity (PWV), and
circulating pro-inflammatory factors. Projects 1 and 2 show that animal models of ELS have hypertension
sensitization, increased sympathetic drive, vascular dysfunction, and activation of pro-inflammatory
macrophages that are known drivers of CVD risk. There are gaps in our knowledge of how ELS affects indicators
for future CVD risk in adolescence, and whether the same pathways in animal models of ELS are associated
with CVD risk in people. Therefore, the principal focus of Project 3 is to address these gaps during
adolescence to identify critical clinical features and molecular pathways in ELS-associated CVD risk, with the
potential to guide early interventions to prevent or mitigate CVD. Our preliminary data further support the
rationale for Project 3, showing that adolescents with ELS have increased vascular stiffness and ambulatory
diastolic BP along with pro-inflammatory metabolite patterns in plasma and gene methylation patterns in
circulating monocytes. The central hypothesis of Project 3 is that ELS promotes vascular stiffness and
abnormal ambulatory BP in adolescents through pro-inflammatory reprogramming of the circulating metabolome
and monocyte epigenome. Our cross-sectional study design utilizes comprehensive cardiovascular and multi-
omics profiling in racially diverse adolescent girls and boys in Alabama. Aim 1 will test the hypothesis that
adolescents exposed to ELS will have increased vascular stiffness and ambulatory blood pressure. Collaborative
experiments will also compare differences in CVD risk indicators in adolescents (Project 3) vs. adults (Project
4) and study heart rate and BP variability as surrogates for increased sympathetic drive along with Project 2.
Aim 2 will test the hypothesis that ELS is associated with pro-inflammatory patterns in the plasma metabolome
and monocyte epigenome in adolescents. Collaborative experiments will specifically focus on short chain fatty
acids (SCFA) and methylation of HDAC9 and NOX2 genes as in animal models of ELS from Projects 1 and 2.
We will integrate our metabolome and methylome data in adolescents with complementary microbiome,
metabolome, and transcriptome data in adults from Project 4 to discover new multi-omic pathways that link ELS
with vascular dysfunction from adolescence to adulthood. Project 3 is conceptually innovative by testing our
central hypothesis in adolescents to help identify targets for future intervention studies to prevent ELS-associated
CVD. The proposed work has translational relevance by applying basic science...

## Key facts

- **NIH application ID:** 10788328
- **Project number:** 5P01HL158500-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Michael Edward Seifert
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $335,551
- **Award type:** 5
- **Project period:** 2023-02-15 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10788328

## Citation

> US National Institutes of Health, RePORTER application 10788328, Early Life Stress-induced Reprogramming of Ambulatory Blood Pressure and Vascular Function in Adolescence (5P01HL158500-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10788328. Licensed CC0.

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