# Delineating Mechanisms of Impaired Vasoreactivity in Thermoneutrality

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2023 · —

## Abstract

Cardiovascular disease (CVD) has a devastating impact on Veteran health and is a leading cause of
both hospitalization and death. Early pathology of CVD is characterized by impaired vasoreactivity (constriction
and dilation). As the vasculature serves the critical functions of distributing nutrients and regulating blood
pressure, it is important to target early dysfunction in the vascular to further understand and prevent this
chronic pathology. We recently housed rats at thermoneutral (TN) conditions and observed debilitated
vasoreactivity along with high blood pressure in females, resulting in an animal model well-suited to further
CVD investigation along with sex differences in pathology. Perivascular adipose tissue (PVAT), considered
brown adipose tissue (BAT), surrounds and regulates the vasculature. Remodeling of PVAT, or the change in
PVAT phenotype from BAT to white adipose tissue (WAT), may cause dysfunction in PVAT’s paracrine
signaling to the vessel. In a preliminary study, we housed rats at either room temperature (RT) or TN and
investigated their own PVAT or PVAT from the oppositely- housed animals along with each rat’s own aorta for
vasoreactivity ex situ. In aorta of TN-housed animals analyzed with PVAT from RT-housed animals, the
vessels showed a significant increase in vasodilation capacity, strongly suggesting that PVAT not only
regulates vasoreactivity, but can repair consistently observed TN-induced diminished dilation. We hypothesize
that PVAT whitening results in diminished paracrine signaling mechanisms to the vasculature, causing
damaged vasoreactivity. Furthermore, sex as a biological variable determines the pathology of diminished
PVAT and vasculature crosstalk. We will determine whether dysfunction in vascular tissue is governed by
altered PVAT paracrine signaling associated with PVAT whitening, define the impact of estrogen on PVAT
whitening and vascular dysfunction, and elucidate whether PVAT remodeling drives altered β-adrenergic-
induced response to temperature. Experimental results supporting these aims will not only generate novel data
on TN-induced PVAT regulation of vasculature and mitochondrial metabolism in female and male rats, but also
pinpoint sex differences in treatment modalities for impaired vascular function in all Veterans with CVD.

## Key facts

- **NIH application ID:** 10701111
- **Project number:** 1I01BX005840-01A2
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Amy Celeste Keller
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10701111

## Citation

> US National Institutes of Health, RePORTER application 10701111, Delineating Mechanisms of Impaired Vasoreactivity in Thermoneutrality (1I01BX005840-01A2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10701111. Licensed CC0.

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