# Perivascular Adipose Tissue (PVAT) as a Central Integrator of Vascular Health

> **NIH NIH P01** · MICHIGAN STATE UNIVERSITY · 2024 · $2,639,839

## Abstract

Summary - Overall
 Vascular health is essential to the normal regulation of cardiovascular function. That dysfunctions of blood
pressure regulation, such as hypertension, remain difficult to treat suggests that the scientific community does
not fully understand the mechanisms by which normal and pathological changes in blood pressure are achieved,
nor how the vasculature can both influence and be impacted by changes in blood pressure. This new Program
Project Grant is based on the overall hypothesis that perivascular adipose tissue (PVAT) has bidirectional
interactions with the other layers of a blood vessel and is a critical partner with these layers to form an integrated
system that maintains vascular health. Our collective preliminary work has led to the hypothesis that PVAT
and its primary components – the adipocyte and progenitor cells, the immune cells, and neuronal
innervation/neurohumoral control —are central integrators of overall vascular health/function. This grant
will enable foundational studies that are critical to understanding how the elements of PVAT work together, and
ultimately influence vascular tone. This grant is unique in that it will also interrogate how (patho)physiological
challenges (e.g. change in stretch, pressure) placed on a vessel affect PVAT function. Our studies will progress
to a model of high fat (HF)-diet induced hypertension, a situation of elevated vascular pressure and PVAT
burden. This work will use models that allow for the most rigorous experimentation: mice in nerve- and adipocyte
progenitor lineage-tracing; optogenetic and chemogenetic approaches; rats as a model organism for HF-diet
induced hypertension; pressure imposition through a novel mid-thoracic aortic coarcted model; novel
microscopic and bioinformatic work; and human vasculature + PVAT for translational potential. Our collective,
novel approach contrasts directly with the plethora of literature that investigates how the PVAT secretome
influences vascular function. We will determine, through projects supported by four cores (administrative,
animal, bioinformatic and microscopy), whether: 1) PVAT possesses the ability to mechanotransduce and has
significant stiffness that contributes to vascular stiffness; 2) PVAT is innervated or under neurohumoral control
with functional consequence; 3) whether the unique microenvironment of PVAT influences immune cell function;
and 4) how the fate of adipocyte progenitors is influenced by vascular stretch. Investigators are deeply
invested in the planning of, execution of and learning from experiments carried out in projects and cores
other than theirs; this work was purposefully developed in this way to be synergistic. This integrated
work advances human health by redefining the functional vessel, a redefinition that could have significant impact
on not only hypertension but all physiologies and dysfunctions which involve the vasculature.

## Key facts

- **NIH application ID:** 10747950
- **Project number:** 5P01HL152951-03
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Stephanie W Watts
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,639,839
- **Award type:** 5
- **Project period:** 2021-12-22 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747950

## Citation

> US National Institutes of Health, RePORTER application 10747950, Perivascular Adipose Tissue (PVAT) as a Central Integrator of Vascular Health (5P01HL152951-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10747950. Licensed CC0.

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