# Systemic vasculature remodeling in females:  effects of the immune system and experience of pregnancy

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2021 · $390,000

## Abstract

Heart disease is a significant killer of women in the United States. Heart disease is different in women
as compared to men, and while hormonal milieu likely contributes to sex-specific cardiovascular physiology,
the understanding of other mitigating factors is critical for the overall health. Epidemiologic data supports the
idea that pregnancy is a driver of cardiovascular health risk. The physiologic stress of pregnancy reveals
inherent cardiovascular strengths or deficiencies, enhances protective mechanisms, or has the potential to
cause damage with cardiovascular consequences. Moreover, pregnancy-induced vascular adaptations
continue postpartum (PP). The work proposed in this application stems from the basic idea that examination of
cardiovascular biology soon after pregnancy is completed will give clues to the cardiovascular adaptations that
persist long-term and therefore affect future cardiovascular disease risk. Study of these persistent adaptations
is therefore expected to delineate mechanisms of sex-specific differences in cardiovascular biology.
 T cells play a role in hypertension and cardiovascular disease. Although pregnancy is a state of
significant changes in the T cell pool, the PP status of these changes has not been completely elucidated, nor
has it been examined in the context of maternal cardiovascular parameters. The PIs of this application are
experts in the maternal immune system and in vascular biology and have partnered to provide preliminary
evidence in a mouse model that immune deficiency in recombinase 1 deficient mice (Rag1-/-) modifies PP
resistance vasculature physiology. The working model is that pregnancy generates T cells that are enhanced
in their ability accumulate in perivascular tissues, that pregnancy increases the ability of vascular cells to
interact with and respond to signals generated by T cells, and that this acquired state underlies the differences
observed PP in vessels from normal and immune deficient animals. This R01 application proposes the
following aims to test a specific model:
Aim 1) Delineate the molecular mechanisms underlying PP perivascular tissue accumulation of T cells and
macrophages and determine their role in PP vascular remodeling and function
Aim 2) Determine the molecular basis relating CD8 T cell function to structural changes observed in PP
systemic vasculature
Aim 3) Define mechanisms underlying decreased PP vascular responses to Acetylcholine in CD8-reconstituted
Rag1-/- as compared to un-manipulated Rag1-/- mice
 When examined in the context of existing human data, the information obtained will aid in designing
relevant longitudinal studies in women, understanding the mechanisms linking T cell biology to PP vascular
homeostasis, and in developing unique tools to delineate future cardiovascular disease risk in women. The
proposed research addresses NHLBI strategic priorities, including Critical Challenges and Compelling
questions related to sex differences in cardiovascular d...

## Key facts

- **NIH application ID:** 10128488
- **Project number:** 5R01HL141747-04
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** ELIZABETH A. BONNEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128488

## Citation

> US National Institutes of Health, RePORTER application 10128488, Systemic vasculature remodeling in females:  effects of the immune system and experience of pregnancy (5R01HL141747-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10128488. Licensed CC0.

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